{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:53:39Z","timestamp":1790952819702,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011983","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T00:00:00Z","timestamp":1707177600000}}],"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T00:00:00Z","timestamp":1706140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R01 AI139124 and P20 GM103625"],"award-info":[{"award-number":["R01 AI139124 and P20 GM103625"]}]},{"name":"National Institute of Health","award":["R21 AI175738"],"award-info":[{"award-number":["R21 AI175738"]}]},{"DOI":"10.13039\/100002570","name":"American Association of Immunologists","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002570","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The protein basic helix-loop-helix family member e40 (BHLHE40) is a transcription factor recently emerged as a key regulator of host immunity to infections, autoimmune diseases and cancer. In this study, we investigated the role of <jats:italic>Bhlhe40<\/jats:italic> in protective T cell responses to the intracellular bacterium <jats:italic>Chlamydia<\/jats:italic> in the female reproductive tract (FRT). Mice deficient in <jats:italic>Bhlhe40<\/jats:italic> exhibited severe defects in their ability to control <jats:italic>Chlamydia muridarum<\/jats:italic> shedding from the FRT. The heightened bacterial burdens in <jats:italic>Bhlhe40<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice correlated with a marked increase in IL-10-producing T regulatory type 1 (Tr1) cells and decreased polyfunctional CD4 T cells co-producing IFN-\u03b3, IL-17A and GM-CSF. Genetic ablation of IL-10 or functional blockade of IL-10R increased CD4 T cell polyfunctionality and partially rescued the defects in bacterial control in <jats:italic>Bhlhe40<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice. Using single-cell RNA sequencing coupled with TCR profiling, we detected a significant enrichment of stem-like T cell signatures in <jats:italic>Bhlhe40<\/jats:italic>-deficient CD4 T cells, whereas WT CD4 T cells were further down on the differentiation trajectory with distinct effector functions beyond IFN-\u03b3 production by Th1 cells. Altogether, we identified <jats:italic>Bhlhe40<\/jats:italic> as a key molecular driver of CD4 T cell differentiation and polyfunctional responses in the FRT against <jats:italic>Chlamydia<\/jats:italic>.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011983","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T18:47:26Z","timestamp":1706208446000},"page":"e1011983","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["BHLHE40 drives protective polyfunctional CD4 T cell differentiation in the female reproductive tract against Chlamydia"],"prefix":"10.1371","volume":"20","author":[{"given":"Miguel A. B.","family":"Mercado","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles M.","family":"Quick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yejin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5526-8966","authenticated-orcid":true,"given":"Lin-Xi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,1,25]]},"reference":[{"key":"ppat.1011983.ref001","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1146\/annurev-immunol-030409-101212","article-title":"Differentiation of Effector CD4 T Cell Populations","volume":"28","author":"J Zhu","year":"2010","journal-title":"Annu Rev Immunol"},{"key":"ppat.1011983.ref002","doi-asserted-by":"crossref","first-page":"ftab014","DOI":"10.1093\/femspd\/ftab014","article-title":"T cell responses to Chlamydia","volume":"79","author":"D. Helble J","year":"2021","journal-title":"Pathogens and Disease"},{"key":"ppat.1011983.ref003","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.4049\/jimmunol.158.7.3344","article-title":"Immunity to Chlamydia trachomatis is mediated by T helper 1 cells through IFN-gamma-dependent and -independent pathways","volume":"158","author":"LL Perry","year":"1997","journal-title":"The Journal of Immunology"},{"key":"ppat.1011983.ref004","doi-asserted-by":"crossref","first-page":"e1001346","DOI":"10.1371\/journal.ppat.1001346","article-title":"Compensatory T Cell Responses in IRG-Deficient Mice Prevent Sustained Chlamydia trachomatis Infections","volume":"7","author":"J Coers","year":"2011","journal-title":"PLOS Pathogens"},{"key":"ppat.1011983.ref005","doi-asserted-by":"crossref","first-page":"e01417","DOI":"10.1128\/mBio.01417-16","article-title":"Chlamydia trachomatis Is Resistant to Inclusion Ubiquitination and Associated Host Defense in Gamma Interferon-Primed Human Epithelial Cells","volume":"7","author":"AK Haldar","year":"2016","journal-title":"mBio"},{"key":"ppat.1011983.ref006","first-page":"9","article-title":"An Adaptive Chlamydia trachomatis-Specific IFN-\u03b3-Producing CD4+ T Cell Response Is Associated With Protection Against Chlamydia Reinfection in Women","author":"RK Bakshi","year":"2018","journal-title":"Front Immunol"},{"key":"ppat.1011983.ref007","first-page":"e00541","article-title":"Innate IFN-\u03b3 Is Essential for Systemic Chlamydia muridarum Control in Mice, While CD4 T Cell-Dependent IFN-\u03b3 Production Is Highly Redundant in the Female Reproductive Tract","volume":"89","author":"MAB Mercado","year":"2021","journal-title":"Infect Immun"},{"key":"ppat.1011983.ref008","doi-asserted-by":"crossref","first-page":"e1010333","DOI":"10.1371\/journal.ppat.1010333","article-title":"Th1 cells are dispensable for primary clearance of Chlamydia from the female reproductive tract of mice","volume":"18","author":"JA Rixon","year":"2022","journal-title":"PLOS Pathogens"},{"key":"ppat.1011983.ref009","first-page":"339","volume-title":"Current Topics in Developmental Biology","author":"Y Kato","year":"2014"},{"key":"ppat.1011983.ref010","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.it.2020.09.002","article-title":"Transcription Factor Bhlhe40 in Immunity and Autoimmunity","volume":"41","author":"ME Cook","year":"2020","journal-title":"Trends in Immunology"},{"key":"ppat.1011983.ref011","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1084\/jem.20150568","article-title":"IL-1\u2013induced Bhlhe40 identifies pathogenic T helper cells in a model of autoimmune neuroinflammation","volume":"213","author":"C-C Lin","year":"2016","journal-title":"J Exp Med"},{"key":"ppat.1011983.ref012","doi-asserted-by":"crossref","first-page":"e101233","DOI":"10.15252\/embj.2018101233","article-title":"Bhlhe40 and Bhlhe41 transcription factors regulate alveolar macrophage self-renewal and identity","volume":"38","author":"R Rauschmeier","year":"2019","journal-title":"The EMBO Journal"},{"key":"ppat.1011983.ref013","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/s41590-019-0382-5","article-title":"Bhlhe40 mediates tissue-specific control of macrophage proliferation in homeostasis and type 2 immunity","volume":"20","author":"NN Jarjour","year":"2019","journal-title":"Nature Immunology"},{"key":"ppat.1011983.ref014","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1084\/jem.20122387","article-title":"CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response","volume":"210","author":"M Mart\u00ednez-Llordella","year":"2013","journal-title":"Journal of Experimental Medicine"},{"key":"ppat.1011983.ref015","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1084\/jem.20170155","article-title":"The transcription factor Bhlhe40 is a switch of inflammatory versus antiinflammatory Th1 cell fate determination","volume":"215","author":"F Yu","year":"2018","journal-title":"J Exp Med"},{"key":"ppat.1011983.ref016","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.immuni.2019.08.013","article-title":"The Transcription Factor Bhlhe40 Programs Mitochondrial Regulation of Resident CD8+ T Cell Fitness and Functionality","volume":"51","author":"C Li","year":"2019","journal-title":"Immunity"},{"key":"ppat.1011983.ref017","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1084\/jem.20171704","article-title":"Bhlhe40 is an essential repressor of IL-10 during Mycobacterium tuberculosis infection","volume":"215","author":"JP Huynh","year":"2018","journal-title":"J Exp Med"},{"key":"ppat.1011983.ref018","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1038\/ncomms4551","article-title":"Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation","volume":"5","author":"C-C Lin","year":"2014","journal-title":"Nature Communications"},{"key":"ppat.1011983.ref019","doi-asserted-by":"crossref","first-page":"e20211406","DOI":"10.1084\/jem.20211406","article-title":"Bhlhe40 function in activated B and TFH cells restrains the GC reaction and prevents lymphomagenesis","volume":"219","author":"R Rauschmeier","year":"2021","journal-title":"Journal of Experimental Medicine"},{"key":"ppat.1011983.ref020","doi-asserted-by":"crossref","first-page":"e1003707","DOI":"10.1371\/journal.ppat.1003707","article-title":"B cells enhance antigen-specific CD4 T cell priming and prevent bacteria dissemination following Chlamydia muridarum genital tract infection","volume":"9","author":"L-X Li","year":"2013","journal-title":"PLoS Pathog"},{"key":"ppat.1011983.ref021","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.immuni.2013.12.013","article-title":"Toll-like Receptor and Inflammasome Signals Converge to Amplify the Innate Bactericidal Capacity of T Helper 1 Cells","volume":"40","author":"H O\u2019Donnell","year":"2014","journal-title":"Immunity"},{"key":"ppat.1011983.ref022","first-page":"5","article-title":"The Role of Non-Cognate T Cell Stimulation during Intracellular Bacterial Infection","author":"SJ McSorley","year":"2014","journal-title":"Frontiers in Immunology"},{"key":"ppat.1011983.ref023","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":"RS Lijek","year":"2018","journal-title":"PNAS"},{"key":"ppat.1011983.ref024","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.4049\/jimmunol.1700914","article-title":"A Chlamydia-Specific TCR-Transgenic Mouse Demonstrates Th1 Polyfunctionality with Enhanced Effector Function","volume":"199","author":"TB Poston","year":"2017","journal-title":"The Journal of Immunology"},{"key":"ppat.1011983.ref025","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nri2274","article-title":"T-cell quality in memory and protection: implications for vaccine design","volume":"8","author":"RA Seder","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"ppat.1011983.ref026","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nm.f.1774","article-title":"CD8+ T cell efficacy in vaccination and disease","volume":"14","author":"V Appay","year":"2008","journal-title":"Nat Med"},{"key":"ppat.1011983.ref027","doi-asserted-by":"crossref","first-page":"e0128714","DOI":"10.1371\/journal.pone.0128714","article-title":"Pathogen-Specific T Cell Polyfunctionality Is a Correlate of T Cell Efficacy and Immune Protection","volume":"10","author":"A Boyd","year":"2015","journal-title":"PLOS ONE"},{"key":"ppat.1011983.ref028","doi-asserted-by":"crossref","first-page":"e42403","DOI":"10.1371\/journal.pone.0042403","article-title":"Evaluating Cellular Polyfunctionality with a Novel Polyfunctionality Index","volume":"7","author":"M Larsen","year":"2012","journal-title":"PLOS ONE"},{"key":"ppat.1011983.ref029","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/imm.13163","article-title":"The IFITM protein family in adaptive immunity","volume":"159","author":"DC Y\u00e1nez","year":"2020","journal-title":"Immunology"},{"key":"ppat.1011983.ref030","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1600-065X.1994.tb00894.x","article-title":"Identification of Genes Induced during Apoptosis in T Lymphocytes","volume":"142","author":"BA Osborne","year":"1994","journal-title":"Immunological Reviews"},{"key":"ppat.1011983.ref031","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.immuni.2016.07.021","article-title":"T Cell Factor 1-Expressing Memory-like CD8+ T Cells Sustain the Immune Response to Chronic Viral Infections","volume":"45","author":"DT Utzschneider","year":"2016","journal-title":"Immunity"},{"key":"ppat.1011983.ref032","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1084\/jem.20161046","article-title":"CD4+ T cell effector commitment coupled to self-renewal by asymmetric cell divisions","volume":"214","author":"SA Nish","year":"2017","journal-title":"Journal of Experimental Medicine"},{"key":"ppat.1011983.ref033","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.cell.2012.09.016","article-title":"A Validated Regulatory Network for Th17 Cell Specification","volume":"151","author":"M Ciofani","year":"2012","journal-title":"Cell"},{"key":"ppat.1011983.ref034","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.immuni.2011.09.010","article-title":"Interleukin-17C Promotes Th17 Cell Responses and Autoimmune Disease via Interleukin-17 Receptor E","volume":"35","author":"SH Chang","year":"2011","journal-title":"Immunity"},{"key":"ppat.1011983.ref035","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1093\/intimm\/dxs075","article-title":"Calcitonin gene-related peptide enhances experimental autoimmune encephalomyelitis by promoting Th17-cell functions","volume":"24","author":"N Mikami","year":"2012","journal-title":"International Immunology"},{"key":"ppat.1011983.ref036","article-title":"Two sequential activation modules control the differentiation of protective T helper-1 (Th1) cells","author":"PD Krueger","year":"2021","journal-title":"Immunity"},{"key":"ppat.1011983.ref037","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.immuni.2018.12.001","article-title":"The Biology of T Regulatory Type 1 Cells and Their Therapeutic Application in Immune-Mediated Diseases","volume":"49","author":"MG Roncarolo","year":"2018","journal-title":"Immunity"},{"key":"ppat.1011983.ref038","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.4049\/jimmunol.1601045","article-title":"IL-10 Receptor Signaling Is Essential for TR1 Cell Function In Vivo","volume":"198","author":"L Brockmann","year":"2017","journal-title":"The Journal of Immunology"},{"key":"ppat.1011983.ref039","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1128\/IAI.00984-10","article-title":"Interleukin-17 Contributes to Generation of Th1 Immunity and Neutrophil Recruitment during Chlamydia muridarum Genital Tract Infection but Is Not Required for Macrophage Influx or Normal Resolution of Infection","volume":"79","author":"AM Scurlock","year":"2011","journal-title":"Infection and Immunity"},{"key":"ppat.1011983.ref040","doi-asserted-by":"crossref","first-page":"e58565","DOI":"10.1371\/journal.pone.0058565","article-title":"Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity","volume":"8","author":"RDV Miguel","year":"2013","journal-title":"PLOS ONE"},{"key":"ppat.1011983.ref041","doi-asserted-by":"crossref","first-page":"e00614","DOI":"10.1128\/IAI.00614-17","article-title":"B Cell Presentation of Chlamydia Antigen Selects Out Protective CD4\u03b313 T Cells: Implications for Genital Tract Tissue-Resident Memory Lymphocyte Clusters","volume":"86","author":"RM Johnson","year":"2018","journal-title":"Infect Immun"},{"key":"ppat.1011983.ref042","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":"JC Labuda","year":"2018","journal-title":"Immunology Letters"},{"key":"ppat.1011983.ref043","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1038\/s41467-020-15543-y","article-title":"Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4+ T cells to cytokines","volume":"11","author":"E Cano-Gamez","year":"2020","journal-title":"Nat Commun"},{"key":"ppat.1011983.ref044","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41590-020-00836-7","article-title":"Gut CD4 + T cell phenotypes are a continuum molded by microbes, not by T H archetypes","volume":"22","author":"E Kiner","year":"2021","journal-title":"Nature Immunology"},{"key":"ppat.1011983.ref045","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.4049\/jimmunol.162.2.1010","article-title":"IL-10 Gene Knockout Mice Show Enhanced Th1-Like Protective Immunity and Absent Granuloma Formation Following Chlamydia trachomatis Lung Infection","volume":"162","author":"X Yang","year":"1999","journal-title":"The Journal of Immunology"},{"key":"ppat.1011983.ref046","doi-asserted-by":"crossref","first-page":"4212","DOI":"10.4049\/jimmunol.164.8.4212","article-title":"Suppression of Endogenous IL-10 Gene Expression in Dendritic Cells Enhances Antigen Presentation for Specific Th1 Induction: Potential for Cellular Vaccine Development","volume":"164","author":"JU Igietseme","year":"2000","journal-title":"The Journal of Immunology"},{"key":"ppat.1011983.ref047","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.4049\/jimmunol.1002952","article-title":"Immunization with Live and Dead Chlamydia muridarum Induces Different Levels of Protective Immunity in a Murine Genital Tract Model: Correlation with MHC Class II Peptide Presentation and Multifunctional Th1 Cells","volume":"186","author":"H Yu","year":"2011","journal-title":"The Journal of Immunology"},{"key":"ppat.1011983.ref048","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1128\/iai.65.6.2145-2152.1997","article-title":"Dissemination of Chlamydia trachomatis chronic genital tract infection in gamma interferon gene knockout mice","volume":"65","author":"TW Cotter","year":"1997","journal-title":"Infection and Immunity"},{"key":"ppat.1011983.ref049","doi-asserted-by":"crossref","first-page":"e76664","DOI":"10.1371\/journal.pone.0076664","article-title":"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","volume":"8","author":"DW Andrew","year":"2013","journal-title":"PLOS ONE"},{"key":"ppat.1011983.ref050","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1172\/JCI5212","article-title":"GM-CSF\u2013deficient mice are susceptible to pulmonary group B streptococcal infection","volume":"103","author":"AM LeVine","year":"1999","journal-title":"J Clin Invest"},{"key":"ppat.1011983.ref051","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1189\/jlb.1204723","article-title":"Disruption of granulocyte macrophage-colony stimulating factor production in the lungs severely affects the ability of mice to control Mycobacterium tuberculosis infection","volume":"77","author":"M Gonzalez-Juarrero","year":"2005","journal-title":"Journal of Leukocyte Biology"},{"key":"ppat.1011983.ref052","doi-asserted-by":"crossref","first-page":"e1004053","DOI":"10.1371\/journal.ppat.1004053","article-title":"Alveolar Macrophages Are Essential for Protection from Respiratory Failure and Associated Morbidity following Influenza Virus Infection","volume":"10","author":"C Schneider","year":"2014","journal-title":"PLOS Pathogens"},{"key":"ppat.1011983.ref053","first-page":"1","article-title":"Parenteral vaccination protects against transcervical infection with Chlamydia trachomatis and generate tissue-resident T cells post-challenge","volume":"5","author":"NDNT Nguyen","year":"2020","journal-title":"npj Vaccines"},{"key":"ppat.1011983.ref054","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1002\/eji.201545800","article-title":"IL-12-polarized Th1 cells produce GM-CSF and induce EAE independent of IL-23","volume":"45","author":"HM Grifka-Walk","year":"2015","journal-title":"European Journal of Immunology"},{"key":"ppat.1011983.ref055","doi-asserted-by":"crossref","first-page":"6281","DOI":"10.1016\/j.cell.2021.11.018","article-title":"Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity","volume":"184","author":"A Schnell","year":"2021","journal-title":"Cell"},{"key":"ppat.1011983.ref056","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1038\/cdd.2013.130","article-title":"A novel subset of helper T cells promotes immune responses by secreting GM-CSF","volume":"20","author":"J Zhang","year":"2013","journal-title":"Cell Death Differ"},{"key":"ppat.1011983.ref057","doi-asserted-by":"crossref","first-page":"eade3369","DOI":"10.1126\/sciimmunol.ade3369","article-title":"In vitro modeling of CD8+ T cell exhaustion enables CRISPR screening to reveal a role for BHLHE40","volume":"8","author":"JE Wu","year":"2023","journal-title":"Science Immunology"},{"key":"ppat.1011983.ref058","doi-asserted-by":"crossref","first-page":"6911","DOI":"10.4049\/jimmunol.1002596","article-title":"Chlamydia-Specific CD4 T Cell Clones Control Chlamydia muridarum Replication in Epithelial Cells by Nitric Oxide-Dependent and -Independent Mechanisms","volume":"185","author":"K Jayarapu","year":"2010","journal-title":"The Journal of Immunology"},{"key":"ppat.1011983.ref059","first-page":"13","article-title":"The Era of Cytotoxic CD4 T Cells","author":"M Cenerenti","year":"2022","journal-title":"Frontiers in Immunology"},{"key":"ppat.1011983.ref060","doi-asserted-by":"crossref","first-page":"2701","DOI":"10.1016\/j.immuni.2021.11.015","article-title":"Cytotoxic CD4+ T cells in cancer: Expanding the immune effector toolbox","volume":"54","author":"DY Oh","year":"2021","journal-title":"Immunity"},{"key":"ppat.1011983.ref061","first-page":"e00367","article-title":"Bhlhe40 limits early IL-10 production from CD4+ T cells during Plasmodium yoelii 17X infection","volume":"0","author":"KA O\u2019Neal","year":"2023","journal-title":"Infection and Immunity"},{"key":"ppat.1011983.ref062","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1128\/iai.65.8.3065-3073.1997","article-title":"Mouse strain-dependent variation in the course and outcome of chlamydial genital tract infection is associated with differences in host response","volume":"65","author":"T Darville","year":"1997","journal-title":"Infection and Immunity"},{"key":"ppat.1011983.ref063","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.4049\/jimmunol.1601314","article-title":"CCR7 Deficiency Allows Accelerated Clearance of Chlamydia from the Female Reproductive Tract","volume":"199","author":"L-X Li","year":"2017","journal-title":"J Immunol"},{"key":"ppat.1011983.ref064","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/cyto.a.21015","article-title":"SPICE: Exploration and analysis of post-cytometric complex multivariate datasets","volume":"79A","author":"M Roederer","year":"2011","journal-title":"Cytometry Part A"},{"key":"ppat.1011983.ref065","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Y Hao","year":"2021","journal-title":"Cell"},{"key":"ppat.1011983.ref066","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nbt.2859","article-title":"The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells","volume":"32","author":"C Trapnell","year":"2014","journal-title":"Nat Biotechnol"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1011983","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T00:00:00Z","timestamp":1707177600000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011983","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T18:46:22Z","timestamp":1707245182000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011983"}},"subtitle":[],"editor":[{"given":"Guangming","family":"Zhong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,1,25]]},"references-count":66,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011983","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1011983","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,25]]}}}