{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:01:08Z","timestamp":1793152868598,"version":"4.5.0"},"reference-count":118,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Disease","award":["T32 AI0078538"],"award-info":[{"award-number":["T32 AI0078538"]}]},{"name":"National Institute of Allergy and Infectious Disease","award":["F31 AI179064"],"award-info":[{"award-number":["F31 AI179064"]}]},{"name":"National Institute of Allergy and Infectious Disease","award":["R01 AI166360"],"award-info":[{"award-number":["R01 AI166360"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Chlamydia trachomatis (Ct) is an obligate intracellular pathogen that causes the most commonly diagnosed bacterial sexually transmitted infection (STI) and is a leading cause of preventable blindness globally. Ct infections can generate a strong pro-inflammatory immune response, leading to immune-mediated pathology in infected tissues. Neutrophils play an important role in mediating both pathology and protection during infection. Excessive neutrophil activation, migration, and survival are associated with host tissue damage during Chlamydia infections. In contrast, neutrophils also perform phagocytic killing of Chlamydia in the presence of IFN-\u03b3 and anti-Chlamydia antibodies. Neutrophil extracellular traps (NETs) and many neutrophil degranulation products have also demonstrated strong anti-Chlamydia functions. To counteract this neutrophil-mediated protection, Chlamydia has developed several evasion strategies. Various Chlamydia proteins can limit potentially protective neutrophil responses by directly targeting receptors present on the surface of neutrophils or neutrophil degranulation products. In this review, we provide a survey of current knowledge regarding the role of neutrophils in pathogenesis and protection, including the ways that Chlamydia circumvents neutrophil functions, and we propose critical areas for future research.<\/jats:p>","DOI":"10.3390\/pathogens14020112","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T09:01:13Z","timestamp":1737622873000},"page":"112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pathogenic and Protective Roles of Neutrophils in Chlamydia trachomatis Infection"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2201-5877","authenticated-orcid":false,"given":"Zoe E. R.","family":"Wilton","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5342-4059","authenticated-orcid":false,"given":"Andzoa N.","family":"Jamus","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4933-6598","authenticated-orcid":false,"given":"Susan B.","family":"Core","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn M.","family":"Frietze","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/nrmicro.2016.30","article-title":"Chlamydia Cell Biology and Pathogenesis","volume":"14","author":"Elwell","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1128\/jb.105.1.355-360.1971","article-title":"Electron Microscopic Observations on the Structure of the Envelopes of Mature Elementary Bodies and Developmental Reticulate Forms of Chlamydia psittaci","volume":"105","author":"Tamura","year":"1971","journal-title":"J. Bacteriol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1136\/ard.2005.044966","article-title":"Persistent Infection of Chlamydia in Reactive Arthritis","volume":"65","author":"Rihl","year":"2006","journal-title":"Ann. Rheum. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1099\/00221287-100-1-31","article-title":"The Developmental Cycle of Chlamydia trachomatis in McCoy Cells Treated with Cytochalasin B","volume":"100","author":"Stirling","year":"1977","journal-title":"J. Gen. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1099\/00221287-135-5-1153","article-title":"The Development of Chlamydia trachomatis Inclusions within the Host Eukaryotic Cell during Interphase and Mitosis","volume":"135","author":"Campbell","year":"1989","journal-title":"Microbiology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1099\/jmm.0.024877-0","article-title":"Innate Immunity in the Male Genital Tract: Chlamydia trachomatis Induces Keratinocyte-Derived Chemokine Production in Prostate, Seminal Vesicle and Epididymis\/Vas Deferens Primary Cultures","volume":"60","author":"Maccioni","year":"2011","journal-title":"J. Med. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e00654-20","DOI":"10.1128\/mSphere.00654-20","article-title":"Antibodies to Variable Domain 4 Linear Epitopes of the Chlamydia trachomatis Major Outer Membrane Protein Are Not Associated with Chlamydia Resolution or Reinfection in Women","volume":"5","author":"Collar","year":"2020","journal-title":"mSphere"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"548","DOI":"10.2471\/BLT.18.228486","article-title":"Chlamydia, Gonorrhoea, Trichomoniasis and Syphilis: Global Prevalence and Incidence Estimates, 2016","volume":"97","author":"Rowley","year":"2019","journal-title":"Bull. World Health Organ."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.clindermatol.2023.12.002","article-title":"The Global Burden of Sexually Transmitted Infections","volume":"42","author":"Sinka","year":"2024","journal-title":"Clin. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Collar, A.L., Linville, A.C., Core, S.B., and Frietze, K.M. (2022). Epitope-Based Vaccines against the Chlamydia trachomatis Major Outer Membrane Protein Variable Domain 4 Elicit Protection in Mice. Vaccines, 10.","DOI":"10.3390\/vaccines10060875"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1097\/OLQ.0b013e3181a2a933","article-title":"Repeat Infection With Chlamydia and Gonorrhea Among Females: A Systematic Review of the Literature","volume":"36","author":"Hosenfeld","year":"2009","journal-title":"Sex. Transm. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1097\/OLQ.0b013e31815c11fe","article-title":"Chlamydia trachomatis Reinfection Rates Among Female Adolescents Seeking Rescreening in School-Based Health Centers","volume":"35","author":"Gaydos","year":"2008","journal-title":"Sex. Transm. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1080\/14760584.2021.1899817","article-title":"Chlamydia trachomatis Vaccines for Genital Infections: Where Are We and How Far Is There to Go?","volume":"20","author":"Darville","year":"2021","journal-title":"Expert. Rev. Vaccines"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1128\/CMR.00105-13","article-title":"Genital Chlamydia trachomatis: Understanding the Roles of Innate and Adaptive Immunity in Vaccine Research","volume":"27","author":"Vasilevsky","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/S0091-7435(02)00058-0","article-title":"Asymptomatic Sexually Transmitted Diseases: The Case for Screening","volume":"36","author":"Farley","year":"2003","journal-title":"Prev. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S1473-3099(19)30279-8","article-title":"Safety and Immunogenicity of the Chlamydia Vaccine Candidate CTH522 Adjuvanted with CAF01 Liposomes or Aluminium Hydroxide: A First-in-Human, Randomised, Double-Blind, Placebo-Controlled, Phase 1 Trial","volume":"19","author":"Abraham","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6979","DOI":"10.1128\/IAI.68.12.6979-6987.2000","article-title":"Immunity to Murine Chlamydia Trachomatis Genital Tract Reinfection Involves B Cells and CD4+ T Cells but Not CD8+ T Cells","volume":"68","author":"Morrison","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7536","DOI":"10.4049\/jimmunol.175.11.7536","article-title":"A Predominant Role for Antibody in Acquired Immunity to Chlamydial Genital Tract Reinfection","volume":"175","author":"Morrison","year":"2005","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4374","DOI":"10.1128\/IAI.00622-10","article-title":"CD4+ T Cells and Antibody Are Required for Optimal Major Outer Membrane Protein Vaccine-Induced Immunity to Chlamydia Muridarum Genital Infection","volume":"78","author":"Farris","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1093\/infdis\/jiv137","article-title":"Protection Against Chlamydia trachomatis Infection and Upper Genital Tract Pathological Changes by Vaccine-Promoted Neutralizing Antibodies Directed to the VD4 of the Major Outer Membrane Protein","volume":"212","author":"Olsen","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Redgrove, K.A., and McLaughlin, E.A. (2014). The Role of the Immune Response in Chlamydia trachomatis Infection of the Male Genital Tract: A Double-Edged Sword. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00534"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e13103","DOI":"10.1111\/aji.13103","article-title":"Anti-chlamydia IgG and IgA Are Insufficient to Prevent Endometrial Chlamydia Infection in Women, and Increased Anti-chlamydia IgG Is Associated with Enhanced Risk for Incident Infection","volume":"81","author":"Darville","year":"2019","journal-title":"Am. J. Rep. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4029","DOI":"10.1128\/IAI.05535-11","article-title":"Enhanced Neutrophil Longevity and Recruitment Contribute to the Severity of Oviduct Pathology during Chlamydia muridarum Infection","volume":"79","author":"Frazer","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3430","DOI":"10.4049\/jimmunol.1301136","article-title":"CD4+ CD25+ Foxp3+ Regulatory T Cells Promote Th17 Responses and Genital Tract Inflammation upon Intracellular Chlamydia muridarum Infection","volume":"191","author":"Fraser","year":"2013","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6704","DOI":"10.1128\/IAI.68.12.6704-6711.2000","article-title":"Infection of Human Monocyte-Derived Macrophages with Chlamydia trachomatis Induces Apoptosis of T Cells: A Potential Mechanism for Persistent Infection","volume":"68","author":"Jendro","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zuck, M., Ellis, T., Venida, A., and Hybiske, K. (2017). Extrusions Are Phagocytosed and Promote Chlamydia Survival within Macrophages: Extrusions Are Phagocytosed and Promote Chlamydia Survival within Macrophages. Cell. Microbiol., 19.","DOI":"10.1101\/041079"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.1128\/IAI.05022-11","article-title":"Tumor Necrosis Factor Alpha Production from CD8+ T Cells Mediates Oviduct Pathological Sequelae Following Primary Genital Chlamydia muridarum Infection","volume":"79","author":"Murthy","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.imlet.2018.08.002","article-title":"Diversity in the T Cell Response to Chlamydia-Sum Are Better than One","volume":"202","author":"Labuda","year":"2018","journal-title":"Immunol. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1128\/iai.52.3.664-670.1986","article-title":"Interaction between Chlamydia spp. and Human Polymorphonuclear Leukocytes in Vitro","volume":"52","author":"Register","year":"1986","journal-title":"Infect. Immun."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gierlikowska, B., Stachura, A., Gierlikowski, W., and Demkow, U. (2021). Phagocytosis, Degranulation and Extracellular Traps Release by Neutrophils\u2014The Current Knowledge, Pharmacological Modulation and Future Prospects. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.666732"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.celrep.2014.06.044","article-title":"A Myeloperoxidase-Containing Complex Regulates Neutrophil Elastase Release and Actin Dynamics during NETosis","volume":"8","author":"Metzler","year":"2014","journal-title":"Cell Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12964-022-00824-4","article-title":"Neutrophil Degranulation and Myocardial Infarction","volume":"20","author":"Zhang","year":"2022","journal-title":"Cell Commun. Signal"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1086\/323341","article-title":"Chlamydia trachomatis Infection Induces Mucosal Addressin Cell Adhesion Molecule\u20131 and Vascular Cell Adhesion Molecule\u20131, Providing an Immunologic Link between the Fallopian Tube and Other Mucosal Tissues","volume":"184","author":"Kelly","year":"2001","journal-title":"J. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/ni0410-282","article-title":"Rolling Back Neutrophil Adhesion","volume":"11","author":"McEver","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1111\/jcmm.12102","article-title":"A Novel Human Anti- VCAM -1 Monoclonal Antibody Ameliorates Airway Inflammation and Remodelling","volume":"17","author":"Lee","year":"2013","journal-title":"J. Cell. Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Rosales, C. (2018). Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types?. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00113"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/nri.2017.105","article-title":"Neutrophil Extracellular Traps in Immunity and Disease","volume":"18","author":"Papayannopoulos","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.micinf.2003.09.014","article-title":"Phagocytosis by Neutrophils","volume":"5","author":"Lee","year":"2003","journal-title":"Microbes Infect."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Manfredi, A.A., Ramirez, G.A., Rovere-Querini, P., and Maugeri, N. (2018). The Neutrophil\u2019s Choice: Phagocytose vs Make Neutrophil Extracellular Traps. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00288"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1242\/jcs.02876","article-title":"Mechanics of Neutrophil Phagocytosis: Experiments and Quantitative Models","volume":"119","author":"Herant","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1083\/jcb.110.5.1555","article-title":"Cytosolic Free Calcium Elevation Mediates the Phagosome-Lysosome Fusion during Phagocytosis in Human Neutrophils","volume":"110","author":"Jaconi","year":"1990","journal-title":"J. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/omi.12252","article-title":"The Roles of NADPH Oxidase in Modulating Neutrophil Effector Responses","volume":"34","author":"Zeng","year":"2019","journal-title":"Mol. Oral Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.clim.2005.07.001","article-title":"Fc\u03b3RIIa Is a Target for Modulation by TNF\u03b1 in Human Neutrophils","volume":"117","author":"Belostocki","year":"2005","journal-title":"Clin. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.4049\/jimmunol.147.6.1823","article-title":"The Effects of IL-1, IL-2, and Tumor Necrosis Factor on Polymorphonuclear Leukocyte Fc Gamma Receptor-Mediated Phagocytosis. IL-2 down-Regulates the Effect of Tumor Necrosis Factor","volume":"147","author":"Simms","year":"1991","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Boero, E., Gorham, R.D., Francis, E.A., Brand, J., Teng, L.H., Doorduijn, D.J., Ruyken, M., Muts, R.M., Lehmann, C., and Verschoor, A. (2023). Purified Complement C3b Triggers Phagocytosis and Activation of Human Neutrophils via Complement Receptor 1. Sci. Rep., 13.","DOI":"10.1038\/s41598-022-27279-4"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil Extracellular Traps Kill Bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Gigon, L., Fettrelet, T., Miholic, M., McLeish, K.R., Yousefi, S., Stojkov, D., and Simon, H.-U. (2023). Syntaxin-4 and SNAP23 Are Involved in Neutrophil Degranulation, but Not in the Release of Mitochondrial DNA during NET Formation. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1272699"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3103\/S0096392520040112","article-title":"Neutrophil Extracellular Traps: New Aspects","volume":"75","author":"Vorobjeva","year":"2020","journal-title":"Mosc. Univ. Biol. Sci. Bull."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Rochael, N.C., Guimar\u00e3es-Costa, A.B., Nascimento, M.T.C., DeSouza-Vieira, T.S., Oliveira, M.P., Garcia e Souza, L.F., Oliveira, M.F., and Saraiva, E.M. (2015). Classical ROS-Dependent and Early\/Rapid ROS-Independent Release of Neutrophil Extracellular Traps Triggered by Leishmania Parasites. Sci. Rep., 5.","DOI":"10.1038\/srep18302"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7413","DOI":"10.4049\/jimmunol.1000675","article-title":"A Novel Mechanism of Rapid Nuclear Neutrophil Extracellular Trap Formation in Response to Staphylococcus aureus","volume":"185","author":"Pilsczek","year":"2010","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1038\/nm.2847","article-title":"Infection-Induced NETosis Is a Dynamic Process Involving Neutrophil Multitasking in Vivo","volume":"18","author":"Yipp","year":"2012","journal-title":"Nat. Med."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Eichelberger, K.R., and Goldman, W.E. (2020). Manipulating Neutrophil Degranulation as a Bacterial Virulence Strategy. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1009054"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1755-1536-6-11","article-title":"Neutrophil Roles in Left Ventricular Remodeling Following Myocardial Infarction","volume":"6","author":"Ma","year":"2013","journal-title":"Fibrogenesis Tissue Repair."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"233","DOI":"10.2147\/JIR.S234710","article-title":"Human Neutrophil Elastase Proteolytic Activity in Ulcerative Colitis Favors the Loss of Function of Therapeutic Monoclonal Antibodies","volume":"13","author":"Curciarello","year":"2020","journal-title":"JIR"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.cell.2018.12.002","article-title":"Activated PMN Exosomes: Pathogenic Entities Causing Matrix Destruction and Disease in the Lung","volume":"176","author":"Genschmer","year":"2019","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1016\/j.bbadis.2014.07.026","article-title":"Cathepsin G Activity Lowers Plasma LDL and Reduces Atherosclerosis","volume":"1842","author":"Wang","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/j.1574-695X.2010.00668.x","article-title":"A Link between Neutrophils and Chronic Disease Manifestations of Chlamydia muridarum Urogenital Infection of Mice","volume":"59","author":"Lee","year":"2010","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1073\/pnas.1711356115","article-title":"Pathology after Chlamydia trachomatis Infection Is Driven by Nonprotective Immune Cells That Are Distinct from Protective Populations","volume":"115","author":"Lijek","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1128\/IAI.01257-10","article-title":"Essential Role for Neutrophils in Pathogenesis and Adaptive Immunity in Chlamydia Caviae Ocular Infections","volume":"79","author":"Lacy","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Lundy, S.R., Abney, K., Ellerson, D., Igietseme, J.U., Carroll, D., Eko, F.O., and Omosun, Y.O. (2021). MiR-378b Modulates Chlamydia-Induced Upper Genital Tract Pathology. Pathogens, 10.","DOI":"10.3390\/pathogens10050566"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/nri1551","article-title":"Immunology of Chlamydia Infection: Implications for a Chlamydia trachomatis Vaccine","volume":"5","author":"Brunham","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.micinf.2018.02.007","article-title":"Activation of Neutrophils by Chlamydia trachomatis-Infected Epithelial Cells Is Modulated by the Chlamydial Plasmid","volume":"20","author":"Lehr","year":"2018","journal-title":"Microbes Infect."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1574-695X.2010.00715.x","article-title":"A Role for CXC Chemokine Receptor-2 in the Pathogenesis of Urogenital Chlamydia muridarum Infection in Mice: CXCR2 and Mouse Urogenital Chlamydial Disease","volume":"60","author":"Lee","year":"2010","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41423-020-0412-0","article-title":"Neutrophil Chemoattractant Receptors in Health and Disease: Double-Edged Swords","volume":"17","author":"Metzemaekers","year":"2020","journal-title":"Cell Mol. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1086\/342417","article-title":"Association between Elevated Neutrophil Defensin Levels and Endometritis","volume":"186","author":"Wiesenfeld","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1159\/000284367","article-title":"Neutrophil Apoptosis: Relevance to the Innate Immune Response and Inflammatory Disease","volume":"2","author":"Fox","year":"2010","journal-title":"J. Innate Immun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/imr.12453","article-title":"Clearance of Apoptotic Neutrophils and Resolution of Inflammation","volume":"273","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/imm.13423","article-title":"Neutrophil and Remnant Clearance in Immunity and Inflammation","volume":"165","author":"Singhal","year":"2022","journal-title":"Immunology"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Reot, L., Adapen, C., Cannou, C., Nunez, N., Lakoum, S., Pimienta, C., Lacroix, L., Binois, O., Frydman, N., and Nugeyre, M.-T. (2024). Seminal Plasma Inhibits Chlamydia trachomatis Infection in Vitro, and May Have Consequences on Mucosal Immunity. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-71499-9"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1128\/IAI.00725-09","article-title":"Production of Reactive Oxygen Species Is Turned On and Rapidly Shut Down in Epithelial Cells Infected with Chlamydia trachomatis","volume":"78","author":"Boncompain","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Wang, X., Wu, H., Fang, C., and Li, Z. (2024). Insights into Innate Immune Cell Evasion by Chlamydia trachomatis. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1289644"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Nguyen, G.T., Green, E.R., and Mecsas, J. (2017). Neutrophils to the ROScue: Mechanisms of NADPH Oxidase Activation and Bacterial Resistance. Front. Cell. Infect. Microbiol., 7.","DOI":"10.3389\/fcimb.2017.00373"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1152\/physiol.00029.2013","article-title":"Matrix Metalloproteinase-9: Many Shades of Function in Cardiovascular Disease","volume":"28","author":"Yabluchanskiy","year":"2013","journal-title":"Physiology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7374","DOI":"10.1128\/IAI.69.12.7374-7379.2001","article-title":"Role for Inducible Nitric Oxide Synthase in Protection from Chronic Chlamydia trachomatis Urogenital Disease in Mice and Its Regulation by Oxygen Free Radicals","volume":"69","author":"Ramsey","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5513","DOI":"10.1128\/IAI.00730-06","article-title":"Inhibition of Matrix Metalloproteinases Protects Mice from Ascending Infection and Chronic Disease Manifestations Resulting from Urogenital Chlamydia muridarum Infection","volume":"74","author":"Imtiaz","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/j.micinf.2007.08.010","article-title":"A Role for Matrix Metalloproteinase-9 in Pathogenesis of Urogenital Chlamydia muridarum Infection in Mice","volume":"9","author":"Imtiaz","year":"2007","journal-title":"Microbes Infect."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.bbapap.2011.09.003","article-title":"Regulation of Matrix Metalloproteinases Activity Studied in Human Endometrium as a Paradigm of Cyclic Tissue Breakdown and Regeneration","volume":"1824","author":"Selvais","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)-Proteins Proteom."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6962","DOI":"10.1128\/IAI.73.10.6962-6973.2005","article-title":"Expression of Matrix Metalloproteinases Subsequent to Urogenital Chlamydia muridarum Infection of Mice","volume":"73","author":"Ramsey","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"401","DOI":"10.4049\/jimmunol.1202286","article-title":"In Vivo Processing of CXCL5 (LIX) by Matrix Metalloproteinase (MMP)-2 and MMP-9 Promotes Early Neutrophil Recruitment in IL-1\u03b2\u2013Induced Peritonitis","volume":"190","author":"Song","year":"2013","journal-title":"J. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3340","DOI":"10.4049\/jimmunol.161.7.3340","article-title":"Generation of Biologically Active IL-1\u03b2 by Matrix Metalloproteinases: A Novel Caspase-1-Independent Pathway of IL-1\u03b2 Processing","volume":"161","author":"Mach","year":"1998","journal-title":"J. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1067\/mob.2002.126850","article-title":"Chlamydia trachomatis Enhances the Expression of Matrix Metalloproteinases in an in Vitro Model of the Human Fallopian Tube Infection","volume":"187","author":"Ault","year":"2002","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/jcp.10014","article-title":"Activation of Progelatinase A (MMP-2) by Neutrophil Elastase, Cathepsin G, and Proteinase-3: A Role for Inflammatory Cells in Tumor Invasion and Angiogenesis","volume":"189","author":"Shamamian","year":"2001","journal-title":"J. Cell. Physiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/cyto.a.23353","article-title":"A Flow Cytometry-based Assay to Determine the Phagocytic Activity of Both Clinical and Nonclinical Antibody Samples against Chlamydia trachomatis","volume":"93","author":"Grasse","year":"2018","journal-title":"Cytometry"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e00409-17","DOI":"10.1128\/IAI.00409-17","article-title":"Neutrophils Are Central to Antibody-Mediated Protection against Genital Chlamydia","volume":"85","author":"Naglak","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Yu, H., Geisler, W.M., Dai, C., Gupta, K., Cutter, G., and Brunham, R.C. (2024). Antibody Responses to Chlamydia trachomatis Vaccine Candidate Antigens in Chlamydia-Infected Women and Correlation with Antibody-Mediated Phagocytosis of Elementary Bodies. Front. Cell. Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1342621"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5454","DOI":"10.1038\/s41467-021-25749-3","article-title":"Chlamydia Evasion of Neutrophil Host Defense Results in NLRP3 Dependent Myeloid-Mediated Sterile Inflammation through the Purinergic P2X7 Receptor","volume":"12","author":"Yang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e2812","DOI":"10.1038\/cddis.2017.52","article-title":"The Role of Extracellular Histone in Organ Injury","volume":"8","author":"Silk","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"105137","DOI":"10.1016\/j.micpath.2021.105137","article-title":"The Role of an Enzymatically Inactive CPAF Mutant Vaccination in Chlamydia muridarum Genital Tract Infection","volume":"160","author":"Chen","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1126\/science.aaa8064","article-title":"Neutrophil Extracellular Traps License Macrophages for Cytokine Production in Atherosclerosis","volume":"349","author":"Warnatsch","year":"2015","journal-title":"Science"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Vicetti Miguel, R.D., Quispe Calla, N.E., Pavelko, S.D., and Cherpes, T.L. (2016). Intravaginal Chlamydia trachomatis Challenge Infection Elicits TH1 and TH17 Immune Responses in Mice That Promote Pathogen Clearance and Genital Tract Damage. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162445"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Andrew, D.W., Cochrane, M., Schripsema, J.H., Ramsey, K.H., Dando, S.J., O\u2019Meara, C.P., Timms, P., and Beagley, K.W. (2013). The Duration of Chlamydia muridarum Genital Tract Infection and Associated Chronic Pathological Changes Are Reduced in IL-17 Knockout Mice but Protection Is Not Increased Further by Immunization. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076664"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Schaefer, K., Brown, N., Kaye, P.M., and Lacey, C.J. (2014). Cervico-Vaginal Immunoglobulin G Levels Increase Post-Ovulation Independently of Neutrophils. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114824"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4830","DOI":"10.1128\/iai.64.11.4830-4833.1996","article-title":"Role of Neutrophils in Controlling Early Stages of a Chlamydia trachomatis Infection","volume":"64","author":"Barteneva","year":"1996","journal-title":"Infect. Immun."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Lepanto, M.S., Rosa, L., Paesano, R., Valenti, P., and Cutone, A. (2019). Lactoferrin in Aseptic and Septic Inflammation. Molecules, 24.","DOI":"10.3390\/molecules24071323"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e00094-19","DOI":"10.1128\/mSystems.00094-19","article-title":"Selected Immunological Mediators and Cervical Microbial Signatures in Women with Chlamydia trachomatis Infection","volume":"4","author":"Filardo","year":"2019","journal-title":"mSystems"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1139\/bcb-2016-0049","article-title":"Effect of Bovine Lactoferrin on Chlamydia trachomatis Infection and Inflammation","volume":"95","author":"Sessa","year":"2017","journal-title":"Biochem. Cell Biol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Lang, J., Yang, N., Deng, J., Liu, K., Yang, P., Zhang, G., and Jiang, C. (2011). Inhibition of SARS Pseudovirus Cell Entry by Lactoferrin Binding to Heparan Sulfate Proteoglycans. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023710"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Di Pietro, M., Filardo, S., Romano, S., and Sessa, R. (2019). Chlamydia trachomatis and Chlamydia Pneumoniae Interaction with the Host: Latest Advances and Future Prospective. Microorganisms, 7.","DOI":"10.3390\/microorganisms7050140"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.micinf.2015.02.005","article-title":"Chlamydia-Secreted Protease CPAF Degrades Host Antimicrobial Peptides","volume":"17","author":"Tang","year":"2015","journal-title":"Microbes Infect."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Scott, A., Weldon, S., Buchanan, P.J., Schock, B., Ernst, R.K., McAuley, D.F., Tunney, M.M., Irwin, C.R., Elborn, J.S., and Taggart, C.C. (2011). Evaluation of the Ability of LL-37 to Neutralise LPS In Vitro and Ex Vivo. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026525"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e00503-23","DOI":"10.1128\/iai.00503-23","article-title":"Antibodies from Chlamydia-Infected Individuals Facilitate Phagocytosis via Fc Receptors","volume":"92","author":"Hybiske","year":"2024","journal-title":"Infect. Immun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1365-2567.2004.01849.x","article-title":"Interferon-\u03b3 Activation of Polymorphonuclear Neutrophil Function","volume":"112","author":"Ellis","year":"2004","journal-title":"Immunology"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Wang, Y., and J\u00f6nsson, F. (2019). Expression, Role, and Regulation of Neutrophil Fc\u03b3 Receptors. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01958"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1038\/s41564-018-0182-y","article-title":"Chlamydia trachomatis Paralyses Neutrophils to Evade the Host Innate Immune Response","volume":"3","author":"Rajeeve","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1128\/IAI.00280-16","article-title":"The Chlamydia-Secreted Protease CPAF Promotes Chlamydial Survival in the Mouse Lower Genital Tract","volume":"84","author":"Yang","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1016\/j.vaccine.2007.02.010","article-title":"Intranasal Immunization with Chlamydial Protease-like Activity Factor and CpG Deoxynucleotides Enhances Protective Immunity against Genital Chlamydia muridarum Infection","volume":"25","author":"Cong","year":"2007","journal-title":"Vaccine"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.chom.2011.06.008","article-title":"The Chlamydia Protease CPAF Regulates Host and Bacterial Proteins to Maintain Pathogen Vacuole Integrity and Promote Virulence","volume":"10","author":"Jorgensen","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1084\/jem.193.8.935","article-title":"Identification of a Chlamydial Protease\u2013Like Activity Factor Responsible for the Degradation of Host Transcription Factors","volume":"193","author":"Zhong","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"41320","DOI":"10.1074\/jbc.M110.152280","article-title":"Cleavage of the NF-\u03baB Family Protein P65\/RelA by the Chlamydial Protease-like Activity Factor (CPAF) Impairs Proinflammatory Signaling in Cells Infected with Chlamydiae","volume":"285","author":"Christian","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"24403","DOI":"10.1073\/pnas.2008032117","article-title":"ORAI1 and ORAI2 Modulate Murine Neutrophil Calcium Signaling, Cellular Activation, and Host Defense","volume":"117","author":"Grimes","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.4049\/jimmunol.1900430","article-title":"A Critical Role of Formyl Peptide Receptors in Host Defense against Escherichia coli","volume":"204","author":"Zhang","year":"2020","journal-title":"J. Immunol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e923909-1","DOI":"10.12659\/MSM.923909","article-title":"Chlamydial-Secreted Protease Chlamydia High Temperature Requirement Protein A (cHtrA) Degrades Human Cathelicidin LL-37 and Suppresses Its Anti-Chlamydial Activity","volume":"26","author":"Dong","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.micinf.2018.06.003","article-title":"Chlamydial Plasmid-Encoded Virulence Factor Pgp3 Interacts with Human Cathelicidin Peptide LL-37 to Modulate Immune Response","volume":"21","author":"Hou","year":"2019","journal-title":"Microbes Infect."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"4701","DOI":"10.1128\/IAI.00746-15","article-title":"Chlamydial Plasmid-Encoded Virulence Factor Pgp3 Neutralizes the Antichlamydial Activity of Human Cathelicidin LL-37","volume":"83","author":"Hou","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e00472-21","DOI":"10.1128\/iai.00472-21","article-title":"Chlamydia Deficient in Plasmid-Encoded Glycoprotein 3 (pGP3) as an Attenuated Live Oral Vaccine","volume":"90","author":"Zhou","year":"2022","journal-title":"Infect. Immun."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Wu, X., Lei, L., Gong, S., Chen, D., Flores, R., and Zhong, G. (2011). The Chlamydial Periplasmic Stress Response Serine Protease cHtrA Is Secreted into Host Cell Cytosol. BMC Microbiol., 11.","DOI":"10.1186\/1471-2180-11-87"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"21612","DOI":"10.1016\/S0021-9258(19)36655-4","article-title":"The Induction by Human Interleukin-6 of Apoptosis in the Promonocytic Cell Line U937 and Human Neutrophils","volume":"267","author":"Afford","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Iula, L., Keitelman, I.A., Sabbione, F., Fuentes, F., Guzman, M., Galletti, J.G., Gerber, P.P., Ostrowski, M., Geffner, J.R., and Jancic, C.C. (2018). Autophagy Mediates Interleukin-1\u03b2 Secretion in Human Neutrophils. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00269"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/2\/112\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:34:35Z","timestamp":1759919675000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/2\/112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,23]]},"references-count":118,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["pathogens14020112"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14020112","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,23]]}}}