{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:45:53Z","timestamp":1790552753767,"version":"4.1.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Invasive aspergillosis (IA) is a life-threatening fungal infection for immunocompromised hosts. It is, therefore, necessary to understand the immune pathways that control this infection. Although the primary infection site is the lungs, aspergillosis can disseminate to other organs through unknown mechanisms. Herein we have examined the\n                    <jats:italic>in vivo<\/jats:italic>\n                    role of various complement pathways as well as the complement receptors C3aR and C5aR1 during experimental systemic infection by\n                    <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                    , the main species responsible for IA. We show that C3 knockout (C3\n                    <jats:sup>-\/-<\/jats:sup>\n                    ) mice are highly susceptible to systemic infection of\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    . Intriguingly, C4\n                    <jats:sup>-\/-<\/jats:sup>\n                    and factor B (FB)\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice showed susceptibility similar to the wild-type mice, suggesting that either the complement pathways display functional redundancy during infection (i.e., one pathway compensates for the loss of the other), or complement is activated non-canonically by\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    protease. Our\n                    <jats:italic>in vitro<\/jats:italic>\n                    study substantiates the presence of C3 and C5 cleaving proteases in\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    . Examination of the importance of the terminal complement pathway employing C5\n                    <jats:sup>-\/-<\/jats:sup>\n                    and C5aR1\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice reveals that it plays a vital role in the conidial clearance. This, in part, is due to the increased conidial uptake by phagocytes. Together, our data suggest that the complement deficiency enhances the susceptibility to systemic infection by\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.978152","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T09:07:10Z","timestamp":1663924030000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Protective role of host complement system in Aspergillus fumigatus infection"],"prefix":"10.3389","volume":"13","author":[{"given":"Rajashri","family":"Shende","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Sze Wah","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heikrujam Thoihen","family":"Meitei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girdhari","family":"Lal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taruna","family":"Madan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishukumar","family":"Aimanianda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayanta Kumar","family":"Pal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvind","family":"Sahu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2016.1231278","article-title":"Aspergillosis and stem cell transplantation: An overview of experimental pathogenesis studies","volume":"7","author":"Bader","year":"2016","journal-title":"Virulence"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2017.90","article-title":"Aspergillus fumigatus morphology and dynamic host interactions","volume":"15","author":"van de Veerdonk","year":"2017","journal-title":"Nat Rev Microbiol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuv018","article-title":"The innate immune response to aspergillus fumigatus at the alveolar surface","volume":"39","author":"Margalit","year":"2015","journal-title":"FEMS Microbiol Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s11046-014-9819-4","article-title":"Advances against aspergillosis: Biology, host response, diagnosis and treatment","volume":"178","author":"Askew","year":"2014","journal-title":"Mycopathologia"},{"key":"B5","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.immuni.2012.08.002","article-title":"Regulation of humoral immunity by complement","volume":"37","author":"Carroll","year":"2012","journal-title":"Immunity"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2011.06.004","article-title":"Novel roles of complement in T effector cell regulation","volume":"217","author":"Heeger","year":"2012","journal-title":"Immunobiology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.6.3264","article-title":"Coligation of the b cell receptor with complement receptor type 2 (CR2\/CD21) using its natural ligand C3dg: Activation without engagement of an inhibitory signaling pathway","volume":"174","author":"Lyubchenko","year":"2005","journal-title":"J.Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2010.05.008","article-title":"Role and mechanism of action of complement in regulating T cell immunity","volume":"47","author":"Dunkelberger","year":"2010","journal-title":"Mol.Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1699-0463.1983.tb00001.x","article-title":"Complement-binding antibodies to aspergillus fumigatus in patients with pulmonary aspergillosis","volume":"91","author":"Schonheyder","year":"1983","journal-title":"Acta Pathol Microbiol Immunol Scand B"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.688-693.2000","article-title":"Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition","volume":"68","author":"Neth","year":"2000","journal-title":"Infect.Immun"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038196","article-title":"The interaction pattern of murine serum ficolin-a with microorganisms","volume":"7","author":"Hummelshoj","year":"2012","journal-title":"PLoS One"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-258376","article-title":"Role of complement and fc{gamma} receptors in the protective activity of the long pentraxin PTX3 against aspergillus fumigatus","volume":"116","author":"Moalli","year":"2010","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1128\/iai.57.11.3412-3417.1989","article-title":"Activation of C3 and binding to aspergillus fumigatus conidia and hyphae","volume":"57","author":"Kozel","year":"1989","journal-title":"Infect Immun"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.5.1913-1918.1992","article-title":"Interactions between conidia of aspergillus fumigatus and human complement component C3","volume":"60","author":"Sturtevant","year":"1992","journal-title":"Infect Immun"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.10.7100","article-title":"Aspergillus conidia activate the complement by the mannan-binding lectin C2 bypass mechanism","volume":"181","author":"Dumestre-Perard","year":"2008","journal-title":"J Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1159\/000369493","article-title":"Effective neutrophil phagocytosis of aspergillus fumigatus is mediated by classical pathway complement activation","volume":"7","author":"Braem","year":"2015","journal-title":"J Innate Immun"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00473","article-title":"Complementary roles of the classical and lectin complement pathways in the defense against aspergillus fumigatus","volume":"7","author":"Rosbjerg","year":"2016","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"463794","DOI":"10.1155\/2012\/463794","article-title":"Complement attack against aspergillus and corresponding evasion mechanisms","volume":"2012","author":"Speth","year":"2012","journal-title":"Interdiscip Perspect Infect Dis"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401845","article-title":"A second stimulus required for enhanced antifungal activity of human neutrophils in blood is provided by anaphylatoxin C5a","volume":"194","author":"Hunniger","year":"2015","journal-title":"J Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nri2939","article-title":"Immunity to fungal infections","volume":"11","author":"Romani","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.12.3031-3038.1998","article-title":"The developmentally regulated alb1 gene of aspergillus fumigatus: Its role in modulation of conidial morphology and virulence","volume":"180","author":"Tsai","year":"1998","journal-title":"J Bacteriol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01037-07","article-title":"The opportunistic human pathogenic fungus aspergillus fumigatus evades the host complement system","volume":"76","author":"Behnsen","year":"2008","journal-title":"Infect Immun"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.08.011","article-title":"Immune evasion by acquisition of complement inhibitors: The mould aspergillus binds both factor h and C4b binding protein","volume":"45","author":"Vogl","year":"2008","journal-title":"Mol Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.001476","article-title":"Aspergillus fumigatus conidial metalloprotease Mep1p cleaves host complement proteins","volume":"293","author":"Shende","year":"2018","journal-title":"J Biol Chem"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01353-09","article-title":"Secreted aspergillus fumigatus protease Alp1 degrades human complement proteins C3, C4, and C5","volume":"78","author":"Behnsen","year":"2010","journal-title":"Infect Immun"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1128\/iai.58.5.1476-1478.1990","article-title":"Use of DBA\/2N mice in models of systemic candidiasis and pulmonary and systemic aspergillosis","volume":"58","author":"Hector","year":"1990","journal-title":"Infect Immun"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2010.04.007","article-title":"Differential mechanisms of resistance to sublethal systemic aspergillus fumigatus infection in immunocompetent BALB\/c and C57BL\/6 mice","volume":"216","author":"Mirkov","year":"2011","journal-title":"Immunobiology"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.10.4380-4388.1994","article-title":"Rodletless mutants of aspergillus fumigatus","volume":"62","author":"Thau","year":"1994","journal-title":"Infect Immun"},{"key":"B29","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1034\/j.1600-065X.2001.1800103.x","article-title":"Structure and biology of complement protein C3, a connecting link between innate and acquired immunity","volume":"180","author":"Sahu","year":"2001","journal-title":"Immunol Rev"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000142249.08135.e9","article-title":"Innate immune response in Th1- and Th2-dominant mouse strains","volume":"22","author":"Watanabe","year":"2004","journal-title":"SHOCK"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12501","article-title":"H-ficolin binds aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses","volume":"146","author":"Bidula","year":"2015","journal-title":"Immunology"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.riam.2010.10.003","article-title":"What makes aspergillus fumigatus a successful pathogen? Genes and molecules involved in invasive aspergillosis","volume":"27","author":"Abad","year":"2010","journal-title":"Rev Iberoam Micol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006248","article-title":"Synergy between the classical and alternative pathways of complement is essential for conferring effective protection against the pandemic influenza A(H1N1) 2009 virus infection","volume":"13","author":"Rattan","year":"2017","journal-title":"PLoS Pathog"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens4040722","article-title":"Differential contributions of the complement anaphylotoxin receptors C5aR1 and C5aR2 to the early innate immune response against staphylococcus aureus infection","volume":"4","author":"Horst","year":"2015","journal-title":"Pathogens"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401750","article-title":"The C5a anaphylatoxin receptor (C5aR1) protects against listeria monocytogenes infection by inhibiting type 1 IFN expression","volume":"193","author":"Calame","year":"2014","journal-title":"J Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2018-0075OC","article-title":"Anaphylatoxins enhance recruitment of nonclassical monocytes via chemokines produced by pleural mesothelial cells in tuberculous pleural effusion","volume":"60","author":"Luo","year":"2019","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100034","article-title":"Conserved natural IgM antibodies mediate innate and adaptive immunity against the opportunistic fungus pneumocystis murina","volume":"207","author":"Rapaka","year":"2010","journal-title":"J Exp Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(01)00025-6","article-title":"Role of natural and immune IgM antibodies in immune responses","volume":"37","author":"Boes","year":"2000","journal-title":"Mol Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.12.2381","article-title":"A critical role of natural immunoglobulin m in immediate defense against systemic bacterial infection","volume":"188","author":"Boes","year":"1998","journal-title":"J Exp Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80433-1","article-title":"Disruption of the Cr2 locus results in a reduction in b-1a cells and in an impaired b cell response to T-dependent antigen","volume":"4","author":"Ahearn","year":"1996","journal-title":"Immunity"},{"key":"B41","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.imbio.2013.08.010","article-title":"Oxidative burst and neutrophil elastase contribute to clearance of aspergillus fumigatus pneumonia in mice","volume":"219","author":"Prufer","year":"2014","journal-title":"Immunobiology"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/172.6.1554","article-title":"Interferon-gamma and tumor necrosis factor-alpha protect mice from invasive aspergillosis","volume":"172","author":"Nagai","year":"1995","journal-title":"J Infect Dis"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1086\/322793","article-title":"Impaired antifungal effector activity but not inflammatory cell recruitment in interleukin-6-deficient mice with invasive pulmonary aspergillosis","volume":"184","author":"Cenci","year":"2001","journal-title":"J Infect Dis"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0123171","article-title":"Impaired T cell responsiveness to interleukin-6 in hematological patients with invasive aspergillosis","volume":"10","author":"Camargo","year":"2015","journal-title":"PLoS One"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1080\/13693780600760773","article-title":"Th1\/Th2 in aspergillosis","volume":"44","author":"Stevens","year":"2006","journal-title":"Med Mycol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00233-09","article-title":"Complement C3 plays an essential role in the control of opportunistic fungal infections","volume":"77","author":"Tsoni","year":"2009","journal-title":"Infect Immun"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.012669199","article-title":"The classical pathway is the dominant complement pathway required for innate immunity to streptococcus pneumoniae infection in mice","volume":"99","author":"Brown","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.12.7304-7309.2001","article-title":"Role of the classical pathway of complement activation in experimentally induced polymicrobial peritonitis","volume":"69","author":"Celik","year":"2001","journal-title":"Infect Immun"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002793","article-title":"The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection","volume":"8","author":"Ali","year":"2012","journal-title":"PLoS Pathog"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000249","article-title":"Surviving mousepox infection requires the complement system","volume":"4","author":"Moulton","year":"2008","journal-title":"PLoS Pathog"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28622","article-title":"Bypassing complement: Evolutionary lessons and future implications","volume":"116","author":"Atkinson","year":"2006","journal-title":"J Clin Invest"},{"key":"B52","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.136.8.2994","article-title":"Alternative complement pathway activation by C4b deposited during classical pathway activation","volume":"136","author":"Matsushita","year":"1986","journal-title":"J Immunol"},{"key":"B53","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.143.7.2256","article-title":"Lysis of sensitized sheep erythrocytes in human sera deficient in the second component of complement","volume":"143","author":"Knutzen Steuer","year":"1989","journal-title":"J Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25982","article-title":"Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2","volume":"116","author":"Selander","year":"2006","journal-title":"J Clin Invest"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2009.12.021","article-title":"Resistance of MBL gene-knockout mice to experimental systemic aspergillosis","volume":"128","author":"Clemons","year":"2010","journal-title":"Immunol Lett"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364254","article-title":"Genetic control of susceptibility to candida albicans in susceptible A\/J and resistant C57BL\/6J mice","volume":"6","author":"Tuite","year":"2005","journal-title":"Genes Immun"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.11.009","article-title":"Leukotriene B4-mediated neutrophil recruitment causes pulmonary capillaritis during lethal fungal sepsis","volume":"23","author":"Lee","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B58","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1128\/CMR.9.1.34","article-title":"Activation of the complement system by pathogenic fungi","volume":"9","author":"Kozel","year":"1996","journal-title":"Clin Microbiol Rev"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218815110","article-title":"The receptor for complement component C3a mediates protection from intestinal ischemia-reperfusion injuries by inhibiting neutrophil mobilization","volume":"110","author":"Wu","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030374","article-title":"The proinflammatory mediators C3a and C5a are essential for liver regeneration","volume":"198","author":"Strey","year":"2003","journal-title":"J Exp Med"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0161867","article-title":"C5a induces the synthesis of IL-6 and TNF-alpha in rat glomerular mesangial cells through MAPK signaling pathways","volume":"11","author":"Ji","year":"2016","journal-title":"PLoS One"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0708fje","article-title":"Regulatory role of C5a in LPS-induced IL-6 production by neutrophils during sepsis","volume":"18","author":"Riedemann","year":"2004","journal-title":"FASEB J"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.5.3410","article-title":"C5a and C5a(desArg) enhance the susceptibility of monocyte-derived macrophages to HIV infection","volume":"166","author":"Kacani","year":"2001","journal-title":"J Immunol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-004-0186-y","article-title":"Complement receptors and the shaping of the natural antibody repertoire","volume":"26","author":"Holers","year":"2005","journal-title":"Springer Semin.Immunopathol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1080\/14789940500051417","article-title":"Immunity to aspergillus fumigatus: the basis for immunotherapy and vaccination","author":"Bellocchio","year":"2005","journal-title":"Med Mycol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01001-07","article-title":"Antibody-mediated protection through cross-reactivity introduces a fungal heresy into immunological dogma","volume":"75","author":"Casadevall","year":"2007","journal-title":"Infect Immun"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00212-20","article-title":"Differential interactions of serum and bronchoalveolar lavage fluid complement proteins with conidia of airborne fungal pathogen aspergillus fumigatus","volume":"88","author":"Wong","year":"2020","journal-title":"Infect Immun"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.978152\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T01:59:16Z","timestamp":1676858356000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.978152\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,23]]},"references-count":67,"alternative-id":["10.3389\/fimmu.2022.978152"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.978152","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,23]]},"article-number":"978152"}}