{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:23:26Z","timestamp":1785425006655,"version":"3.56.0"},"reference-count":61,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"publisher","award":["HRZZ-IP-2022-10-8445; HRZZ-IP-2016-06-9003"],"award-info":[{"award-number":["HRZZ-IP-2022-10-8445; HRZZ-IP-2016-06-9003"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"award":["HRZZ-IP-2022-10-8445; HRZZ-IP-2016-06-9003"],"award-info":[{"award-number":["HRZZ-IP-2022-10-8445; HRZZ-IP-2016-06-9003"]}],"id":[{"id":"https:\/\/ror.org\/03n51vw80","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023652","name":"University of Rijeka","doi-asserted-by":"crossref","award":["UNIRI-BIOMED-18-128"],"award-info":[{"award-number":["UNIRI-BIOMED-18-128"]}],"id":[{"id":"10.13039\/501100023652","id-type":"DOI","asserted-by":"crossref"}]},{"award":["UNIRI-BIOMED-18-128"],"award-info":[{"award-number":["UNIRI-BIOMED-18-128"]}],"id":[{"id":"https:\/\/ror.org\/05r8dqr10","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2022-01362"],"award-info":[{"award-number":["2022-01362"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2022-01362"],"award-info":[{"award-number":["2022-01362"]}],"id":[{"id":"https:\/\/ror.org\/03zttf063","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Autophagy is a crucial mechanism in the host response to intracellular bacterial pathogens during which microorganisms may undergo direct degradation in autophagolysosomes. As a highly virulent intracellular pathogen, Francisella tularensis has developed survival strategies to escape from the phagosome, replicate in the cytosol of mononuclear cells, and avoid degradation within the double-membrane vacuole during the autophagy-mediated response. The aim of this study was to investigate the role of the ATG5 autophagy protein in the host immune response to Francisella tularensis subsp. holarctica, live vaccine strain (LVS), since ATG5 plays an important role in autophagosome formation during canonical autophagy. In vitro experiments were conducted on immortalized bone marrow macrophages subjected to starvation-induced autophagy. Transgenic mice deficient in ATG5 of cells of the myeloid lineage (monocytes\/macrophages and granulocytes) were used to analyze the immunological responses after intradermal infection. Cytokine levels were analyzed using Luminex, RT-qPCR, and ELISA, while inflammatory cell infiltration in the lung was analyzed by immunohistochemistry. Our results demonstrate that induced autophagy decreased bacterial replication in vitro. However, ATG5 deficiency in myeloid cells in vivo significantly diminished levels of pro-inflammatory cytokine IFN-\u03b3 in the sera, spleen, liver, and lung during Francisella infection. The attenuated pro-inflammatory response also led to significantly reduced macrophage and T cell infiltration in the lung tissue. Our findings also reveal that neutralization of IL-1\u03b2 in myeloid ATG5\u0394Mye mice increased susceptibility to tularemia by increasing bacterial burden in organs.<\/jats:p>","DOI":"10.3390\/microorganisms14071593","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:17:52Z","timestamp":1784647072000},"page":"1593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulatory Role of ATG5 Protein in Immune Modulation During Experimental Tularemia"],"prefix":"10.3390","volume":"14","author":[{"given":"Mirna","family":"Mihel\u010di\u0107","sequence":"first","affiliation":[{"name":"Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, 51 000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Viduka","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, 51 000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0161a","family":"Antoni\u0107","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, 51 000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreja","family":"Zubkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, 51 000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Mare\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, 51 000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7028-1245","authenticated-orcid":false,"given":"Mateja","family":"O\u017eani\u010d","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, 51 000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjell","family":"Enesl\u00e4tt","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Ume\u00e5 University, SE-901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Abram","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, 51 000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0768-8405","authenticated-orcid":false,"given":"Anders","family":"Sj\u00f6stedt","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Ume\u00e5 University, SE-901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4138-3581","authenticated-orcid":false,"given":"Marina","family":"\u0160anti\u0107","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, 51 000 Rijeka, Croatia"},{"name":"Department of Environmental Health, Teaching Institute of Public Health of Primorje-Gorski Kotar County, 51 000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1126\/science.1099993","article-title":"Autophagy in health and disease: A double-edged sword","volume":"306","author":"Shintani","year":"2004","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40169-017-0154-5","article-title":"Autophagy and inflammation","volume":"6","author":"Qian","year":"2017","journal-title":"Clin. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Merkley, S.D., Chock, C.J., Yang, X.O., Harris, J., and Castillo, E.F. (2018). Modulating T Cell Responses via Autophagy: The Intrinsic Influence Controlling the Function of Both Antigen-Presenting Cells and T Cells. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02914"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1080\/15548627.2015.1107692","article-title":"Atg41\/Icy2 regulates autophagosome formation","volume":"11","author":"Yao","year":"2015","journal-title":"Autophagy"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ye, X., Zhou, X.J., and Zhang, H. (2018). Exploring the Role of Autophagy-Related Gene 5 (ATG5) Yields Important Insights into Autophagy in Autoimmune\/Autoinflammatory Diseases. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02334"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nature09782","article-title":"Autophagy in immunity and inflammation","volume":"469","author":"Levine","year":"2011","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E3168","DOI":"10.1073\/pnas.1210500109","article-title":"Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation","volume":"109","author":"Castillo","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.cell.2004.11.038","article-title":"Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages","volume":"119","author":"Gutierrez","year":"2004","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Dortet, L., Mostowy, S., Samba-Louaka, A., Gouin, E., Nahori, M.A., Wiemer, E.A., Dussurget, O., and Cossart, P. (2011). Recruitment of the major vault protein by InlK: A Listeria monocytogenes strategy to avoid autophagy. PLoS Pathog., 7.","DOI":"10.1371\/annotation\/a70544fc-6d8b-4549-921a-9e86557b0ffc"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1126\/science.1106036","article-title":"Escape of intracellular Shigella from autophagy","volume":"307","author":"Ogawa","year":"2005","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e00865-00814","DOI":"10.1128\/mBio.00865-14","article-title":"Autophagy facilitates Salmonella replication in HeLa cells","volume":"5","author":"Yu","year":"2014","journal-title":"mBio"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.immuni.2009.12.006","article-title":"In vivo requirement for Atg5 in antigen presentation by dendritic cells","volume":"32","author":"Lee","year":"2010","journal-title":"Immunity"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1084\/jem.20061303","article-title":"A critical role for the autophagy gene Atg5 in T cell survival and proliferation","volume":"204","author":"Pua","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.cell.2007.10.035","article-title":"Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice","volume":"131","author":"Komatsu","year":"2007","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.cell.2009.05.023","article-title":"p62 at the crossroads of autophagy, apoptosis, and cancer","volume":"137","author":"Moscat","year":"2009","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.4049\/jimmunol.1601196","article-title":"Atg7 Deficiency Intensifies Inflammasome Activation and Pyroptosis in Pseudomonas Sepsis","volume":"198","author":"Pu","year":"2017","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"a010314","DOI":"10.1101\/cshperspect.a010314","article-title":"Mechanisms of Francisella tularensis intracellular pathogenesis","volume":"3","author":"Celli","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ozanic, M., Marecic, V., Abu Kwaik, Y., and Santic, M. (2015). The Divergent Intracellular Lifestyle of Francisella tularensis in Evolutionarily Distinct Host Cells. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005208"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5940","DOI":"10.1128\/IAI.71.10.5940-5950.2003","article-title":"An attenuated strain of the facultative intracellular bacterium Francisella tularensis can escape the phagosome of monocytic cells","volume":"71","author":"Golovliov","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1111\/j.1462-5822.2005.00529.x","article-title":"Modulation of biogenesis of the Francisella tularensis subsp. novicida-containing phagosome in quiescent human macrophages and its maturation into a phagolysosome upon activation by IFN-gamma","volume":"7","author":"Santic","year":"2005","journal-title":"Cell. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1111\/j.1462-5822.2005.00526.x","article-title":"The Francisella tularensis pathogenicity island protein IglC and its regulator MglA are essential for modulating phagosome biogenesis and subsequent bacterial escape into the cytoplasm","volume":"7","author":"Santic","year":"2005","journal-title":"Cell. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14578","DOI":"10.1073\/pnas.0601838103","article-title":"Autophagy-mediated reentry of Francisella tularensis into the endocytic compartment after cytoplasmic replication","volume":"103","author":"Checroun","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"125","DOI":"10.4161\/auto.5.1.7305","article-title":"Francisella tularensis regulates autophagy-related host cell signaling pathways","volume":"5","author":"Cremer","year":"2009","journal-title":"Autophagy"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Steele, S., Brunton, J., Ziehr, B., Taft-Benz, S., Moorman, N., and Kawula, T. (2013). Francisella tularensis harvests nutrients derived via ATG5-independent autophagy to support intracellular growth. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003562"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6885","DOI":"10.4049\/jimmunol.180.10.6885","article-title":"Macrophage proinflammatory response to Francisella tularensis live vaccine strain requires coordination of multiple signaling pathways","volume":"180","author":"Cole","year":"2008","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1111\/j.1462-5822.2012.01816.x","article-title":"Repression of bacterial lipoprotein production by Francisella novicida facilitates evasion of innate immune recognition","volume":"14","author":"Jones","year":"2012","journal-title":"Cell. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1099\/mic.0.031716-0","article-title":"Restricted cytosolic growth of Francisella tularensis subsp. tularensis by IFN-gamma activation of macrophages","volume":"156","author":"Edwards","year":"2010","journal-title":"Microbiology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S1097-2765(02)00599-3","article-title":"The inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proIL-beta","volume":"10","author":"Martinon","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature09663","article-title":"A role for mitochondria in NLRP3 inflammasome activation","volume":"469","author":"Zhou","year":"2011","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Harris, J. (2013). Autophagy and IL-1 Family Cytokines. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00083"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1073\/pnas.0504271103","article-title":"Internalization and phagosome escape required for Francisella to induce human monocyte IL-1beta processing and release","volume":"103","author":"Gavrilin","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"23844","DOI":"10.1074\/jbc.M113.490086","article-title":"Repression of inflammasome by Francisella tularensis during early stages of infection","volume":"288","author":"Dotson","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kelava, I., Mihelcic, M., Ozanic, M., Marecic, V., Knezevic, M., Curlin, M., Stifter, S., Sjostedt, A., and Santic, M. (2020). Atg5-Deficient Mice Infected with Francisella tularensis LVS Demonstrate Increased Survival and Less Severe Pathology in Internal Organs. Microorganisms, 8.","DOI":"10.3390\/microorganisms8101531"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nature04724","article-title":"Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice","volume":"441","author":"Hara","year":"2006","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1128\/IAI.01322-08","article-title":"T cells from lungs and livers of Francisella tularensis-immune mice control the growth of intracellular bacteria","volume":"77","author":"Collazo","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1128\/IAI.01654-13","article-title":"Identification of early interactions between Francisella and the host","volume":"82","author":"Roberts","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.immuni.2010.02.009","article-title":"Delivery of cytosolic components by autophagic adaptor protein p62 endows autophagosomes with unique antimicrobial properties","volume":"32","author":"Ponpuak","year":"2010","journal-title":"Immunity"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.chom.2008.10.003","article-title":"Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens","volume":"4","author":"Zhao","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1016\/j.vaccine.2004.10.034","article-title":"Aerosol-, but not intradermal-immunization with the live vaccine strain of Francisella tularensis protects mice against subsequent aerosol challenge with a highly virulent type A strain of the pathogen by an alphabeta T cell- and interferon gamma- dependent mechanism","volume":"23","author":"Shen","year":"2005","journal-title":"Vaccine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4701","DOI":"10.1038\/emboj.2011.398","article-title":"Autophagy-based unconventional secretory pathway for extracellular delivery of IL-1beta","volume":"30","author":"Dupont","year":"2011","journal-title":"EMBO J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7709","DOI":"10.4049\/jimmunol.179.11.7709","article-title":"Differential requirements by CD4+ and CD8+ T cells for soluble and membrane TNF in control of Francisella tularensis live vaccine strain intramacrophage growth","volume":"179","author":"Cowley","year":"2007","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3502","DOI":"10.1128\/IAI.00226-08","article-title":"MglA and Igl proteins contribute to the modulation of Francisella tularensis live vaccine strain-containing phagosomes in murine macrophages","volume":"76","author":"Bonquist","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.micinf.2011.05.008","article-title":"Autophagy facilitates an IFN-gamma response and signal transduction","volume":"13","author":"Chang","year":"2011","journal-title":"Microbes Infect."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.smim.2013.10.007","article-title":"The secretion of IL-1beta and options for release","volume":"25","author":"Piccioli","year":"2013","journal-title":"Semin. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.immuni.2012.04.015","article-title":"TBK-1 promotes autophagy-mediated antimicrobial defense by controlling autophagosome maturation","volume":"37","author":"Pilli","year":"2012","journal-title":"Immunity"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.4049\/jimmunol.1401958","article-title":"Atg7 enhances host defense against infection via downregulation of superoxide but upregulation of nitric oxide","volume":"194","author":"Li","year":"2015","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jhep.2015.08.019","article-title":"Macrophage autophagy limits acute toxic liver injury in mice through down regulation of interleukin-1beta","volume":"64","author":"Ilyas","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/nature07383","article-title":"Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production","volume":"456","author":"Saitoh","year":"2008","journal-title":"Nature"},{"key":"ref_50","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-1beta Secretion in Human Neutrophils. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00269"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s41232-019-0101-5","article-title":"The role of interleukin-1 in general pathology","volume":"39","author":"Kaneko","year":"2019","journal-title":"Inflamm. Regen."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.ajpath.2013.07.008","article-title":"IL-10 restrains IL-17 to limit lung pathology characteristics following pulmonary infection with Francisella tularensis live vaccine strain","volume":"183","author":"Slight","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1126\/science.aal3535","article-title":"Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages","volume":"356","author":"Ip","year":"2017","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1084\/jem.20030687","article-title":"Multiple T cell subsets control Francisella tularensis LVS intracellular growth without stimulation through macrophage interferon gamma receptors","volume":"198","author":"Cowley","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5843","DOI":"10.1128\/IAI.01176-08","article-title":"Infected-host-cell repertoire and cellular response in the lung following inhalation of Francisella tularensis Schu S4, LVS, or U112","volume":"76","author":"Hall","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1093\/infdis\/jiy049","article-title":"Interleukin 1alpha (IL-1alpha) Promotes Pathogenic Immature Myeloid Cells and IL-1beta Favors Protective Mature Myeloid Cells During Acute Lung Infection","volume":"217","author":"Periasamy","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/hep.31209","article-title":"Decreased Hepatocyte Autophagy Leads to Synergistic IL-1beta and TNF Mouse Liver Injury and Inflammation","volume":"72","author":"Shen","year":"2020","journal-title":"Hepatology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3526","DOI":"10.1073\/pnas.1322831111","article-title":"IL-1 receptor blockade restores autophagy and reduces inflammation in chronic granulomatous disease in mice and in humans","volume":"111","author":"Smeekens","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"del Barrio, L., Sahoo, M., Lantier, L., Reynolds, J.M., Ceballos-Olvera, I., and Re, F. (2015). Production of anti-LPS IgM by B1a B cells depends on IL-1beta and is protective against lung infection with Francisella tularensis LVS. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004706"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6977","DOI":"10.1128\/JB.00506-06","article-title":"Chromosome rearrangement and diversification of Francisella tularensis revealed by the type B (OSU18) genome sequence","volume":"188","author":"Petrosino","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.4161\/auto.20808","article-title":"Cytosolic clearance of replication-deficient mutants reveals Francisella tularensis interactions with the autophagic pathway","volume":"8","author":"Chong","year":"2012","journal-title":"Autophagy"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/7\/1593\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:21:58Z","timestamp":1784780518000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/7\/1593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":61,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["microorganisms14071593"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14071593","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]}}}