{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:33:30Z","timestamp":1787772810594,"version":"build-2784847793"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009905","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T00:00:00Z","timestamp":1631145600000}}],"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI130763"],"award-info":[{"award-number":["AI130763"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI110783"],"award-info":[{"award-number":["AI110783"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>B1 cells, a subset of B lymphocytes whose developmental origin, phenotype, and function differ from that of conventional B2 cells, are the main source of \u201cnatural\u201d IgM but can also respond to infection by rapidly producing pathogen-specific IgM directed against T-independent antigens. <jats:italic>Francisella tularensis<\/jats:italic> (<jats:italic>Ft<\/jats:italic>) is a Gram-negative bacterium that causes tularemia. Infection with <jats:italic>Ft<\/jats:italic> Live Vaccine Strain activates B1 cells for production of IgM directed against the bacterial LPS in a process incompletely understood. Here we show that immunization with purified <jats:italic>Ft<\/jats:italic> LPS elicits production of LPS-specific IgM and IgG<jats:sub>3<\/jats:sub> by B1 cells independently of TLR2 or MyD88. Immunization, but not infection, generated peritoneum-resident memory B1 cells that differentiated into LPS-specific antibody secreting cells (ASC) upon secondary challenge. IL-5 was rapidly induced by immunization with <jats:italic>Ft<\/jats:italic> LPS and was required for production of LPS-specific IgM. Antibody-mediated depletion of ILC2 indicated that these cells were the source of IL-5 and were required for IgM production. IL-25, an alarmin that strongly activates ILC2, was rapidly secreted in response to immunization or infection and its administration to mice significantly increased IgM production and B1 cell differentiation to ASC. Conversely, mice lacking IL-17RB, the IL-25 receptor, showed impaired IL-5 induction, IgM production, and B1 ASC differentiation in response to immunization. Administration of IL-5 to <jats:italic>Il17rb<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice rescued these B1 cells-mediated responses. <jats:italic>Il17rb<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice were more susceptible to infection with <jats:italic>Ft<\/jats:italic> LVS and failed to develop immunity upon secondary challenge suggesting that LPS-specific IgM is one of the protective adaptive immune mechanisms against tularemia. Our results indicated that immunization with <jats:italic>Ft<\/jats:italic> LPS triggers production of IL-25 that, through stimulation of IL-5 release by ILC2, promotes B1 cells activation and differentiation into IgM secreting cells. By revealing the existence of an IL-25-ILC2-IL-5 axis our results suggest novel strategies to improve vaccination against T-independent bacterial antigens.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009905","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T17:37:51Z","timestamp":1630085871000},"page":"e1009905","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Critical role of IL-25-ILC2-IL-5 axis in the production of anti-Francisella LPS IgM by B1 B cells"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7644-7034","authenticated-orcid":true,"given":"Carlos Henrique D.","family":"Barbosa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3642-7500","authenticated-orcid":true,"given":"Louis","family":"Lantier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3490-0544","authenticated-orcid":true,"given":"Joseph","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1905-4493","authenticated-orcid":true,"given":"Jinyong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1181-0717","authenticated-orcid":true,"given":"Fabio","family":"Re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,8,27]]},"reference":[{"issue":"6021","key":"ppat.1009905.ref001","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1126\/science.1201730","article-title":"Different B cell populations mediate early and late memory during an endogenous immune response","volume":"331","author":"KA Pape","year":"2011","journal-title":"Science (New York, NY)"},{"issue":"10","key":"ppat.1009905.ref002","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1007\/s00018-012-0971-z","article-title":"IgM memory B cells: a mouse\/human paradox","volume":"69","author":"CA Reynaud","year":"2012","journal-title":"Cellular and molecular life sciences: CMLS"},{"issue":"3","key":"ppat.1009905.ref003","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1084\/jem.20111696","article-title":"A germinal center-independent pathway generates unswitched memory B cells early in the primary response","volume":"209","author":"JJ Taylor","year":"2012","journal-title":"The Journal of experimental medicine"},{"issue":"5","key":"ppat.1009905.ref004","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1002\/JLB.3RI0519-161R","article-title":"Secreted IgM: New tricks for an old molecule","volume":"106","author":"R Blandino","year":"2019","journal-title":"Journal of leukocyte biology"},{"key":"ppat.1009905.ref005","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/j.0105-2896.2006.00402.x","article-title":"Protective \u2019immunity\u2019 by pre-existent neutralizing antibody titers and preactivated T cells but not by so-called \u2019immunological memory\u2019","volume":"211","author":"RM Zinkernagel","year":"2006","journal-title":"Immunological reviews"},{"issue":"5447","key":"ppat.1009905.ref006","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1126\/science.286.5447.2156","article-title":"Control of early viral and bacterial distribution and disease by natural antibodies","volume":"286","author":"AF Ochsenbein","year":"1999","journal-title":"Science (New York, NY)"},{"key":"ppat.1009905.ref007","doi-asserted-by":"crossref","first-page":"324","DOI":"10.3389\/fimmu.2016.00324","article-title":"B-1 Cell Heterogeneity and the Regulation of Natural and Antigen-Induced IgM Production","volume":"7","author":"N Baumgarth","year":"2016","journal-title":"Frontiers in immunology"},{"key":"ppat.1009905.ref008","doi-asserted-by":"crossref","first-page":"535","DOI":"10.3389\/fimmu.2014.00535","article-title":"B1b cells recognize protective antigens after natural infection and vaccination","volume":"5","author":"AF Cunningham","year":"2014","journal-title":"Frontiers in immunology"},{"issue":"1","key":"ppat.1009905.ref009","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/eji.201141890","article-title":"B-1 cells in the bone marrow are a significant source of natural IgM","volume":"42","author":"YS Choi","year":"2012","journal-title":"European journal of immunology"},{"issue":"10","key":"ppat.1009905.ref010","doi-asserted-by":"crossref","first-page":"5406","DOI":"10.4049\/jimmunol.171.10.5406","article-title":"Peritoneal cavity B cells are precursors of splenic IgM natural antibody-producing cells","volume":"171","author":"T Kawahara","year":"2003","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"issue":"10","key":"ppat.1009905.ref011","doi-asserted-by":"crossref","first-page":"5518","DOI":"10.4049\/jimmunol.165.10.5518","article-title":"Mac-1-negative B-1b phenotype of natural antibody-producing cells, including those responding to Gal alpha 1,3Gal epitopes in alpha 1,3-galactosyltransferase-deficient mice","volume":"165","author":"H Ohdan","year":"2000","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"issue":"7","key":"ppat.1009905.ref012","doi-asserted-by":"crossref","first-page":"3819","DOI":"10.4049\/jimmunol.170.7.3819","article-title":"The resolution of relapsing fever borreliosis requires IgM and is concurrent with expansion of B1b lymphocytes","volume":"170","author":"KR Alugupalli","year":"2003","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"issue":"3","key":"ppat.1009905.ref013","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.immuni.2004.06.019","article-title":"B1b lymphocytes confer T cell-independent long-lasting immunity","volume":"21","author":"KR Alugupalli","year":"2004","journal-title":"Immunity"},{"issue":"11","key":"ppat.1009905.ref014","doi-asserted-by":"crossref","first-page":"4343","DOI":"10.1073\/pnas.0813411106","article-title":"Antigen-specific B-1a antibodies induced by Francisella tularensis LPS provide long-term protection against F. tularensis LVS challenge","volume":"106","author":"LE Cole","year":"2009","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"14","key":"ppat.1009905.ref015","doi-asserted-by":"crossref","first-page":"5388","DOI":"10.1073\/pnas.1121627109","article-title":"Antigen-specific memory in B-1a and its relationship to natural immunity","volume":"109","author":"Y Yang","year":"2012","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"1","key":"ppat.1009905.ref016","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.immuni.2005.04.011","article-title":"B-1a and B-1b cells exhibit distinct developmental requirements and have unique functional roles in innate and adaptive immunity to S. pneumoniae","volume":"23","author":"KM Haas","year":"2005","journal-title":"Immunity"},{"key":"ppat.1009905.ref017","first-page":"163","article-title":"The role of B-1 and B-2 cells in immune protection from influenza virus infection","volume":"252","author":"N Baumgarth","year":"2000","journal-title":"Current topics in microbiology and immunology"},{"issue":"13","key":"ppat.1009905.ref018","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.1084\/jem.20080979","article-title":"Dual role for B-1a cells in immunity to influenza virus infection","volume":"205","author":"YS Choi","year":"2008","journal-title":"The Journal of experimental medicine"},{"issue":"14","key":"ppat.1009905.ref019","doi-asserted-by":"crossref","first-page":"5382","DOI":"10.1073\/pnas.1121631109","article-title":"Antigen-specific antibody responses in B-1a and their relationship to natural immunity","volume":"109","author":"Y Yang","year":"2012","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"3","key":"ppat.1009905.ref020","doi-asserted-by":"crossref","first-page":"e1004706","DOI":"10.1371\/journal.ppat.1004706","article-title":"Production of anti-LPS IgM by B1a B cells depends on IL-1beta and is protective against lung infection with Francisella tularensis LVS","volume":"11","author":"L del Barrio","year":"2015","journal-title":"PLoS Pathog"},{"issue":"7","key":"ppat.1009905.ref021","doi-asserted-by":"crossref","first-page":"4858","DOI":"10.4049\/jimmunol.180.7.4858","article-title":"Complement factor H-binding protein, a putative virulence determinant of Borrelia hermsii, is an antigenic target for protective B1b lymphocytes","volume":"180","author":"MJ Colombo","year":"2008","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"issue":"24","key":"ppat.1009905.ref022","doi-asserted-by":"crossref","first-page":"9803","DOI":"10.1073\/pnas.0812431106","article-title":"The porin OmpD from nontyphoidal Salmonella is a key target for a protective B1b cell antibody response","volume":"106","author":"C Gil-Cruz","year":"2009","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"3","key":"ppat.1009905.ref023","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1084\/jem.153.3.694","article-title":"Antiphosphocholine antibodies found in normal mouse serum are protective against intravenous infection with type 3 streptococcus pneumoniae","volume":"153","author":"DE Briles","year":"1981","journal-title":"The Journal of experimental medicine"},{"key":"ppat.1009905.ref024","doi-asserted-by":"crossref","first-page":"12651","DOI":"10.1038\/ncomms12651","article-title":"Fat-associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation","volume":"7","author":"LH Jackson-Jones","year":"2016","journal-title":"Nature communications"},{"issue":"4","key":"ppat.1009905.ref025","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1111\/imm.12909","article-title":"Both B-1a and B-1b cells exposed to Mycobacterium tuberculosis lipids differentiate into IgM antibody-secreting cells","volume":"154","author":"C Ordo\u00f1ez","year":"2018","journal-title":"Immunology"},{"key":"ppat.1009905.ref026","doi-asserted-by":"crossref","first-page":"840","DOI":"10.3389\/fimmu.2018.00840","article-title":"Group 2 Innate Lymphoid Cells in Pulmonary Immunity and Tissue Homeostasis","volume":"9","author":"BC Mindt","year":"2018","journal-title":"Frontiers in immunology"},{"issue":"4","key":"ppat.1009905.ref027","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1172\/JCI124606","article-title":"Epithelial cell-derived cytokines: more than just signaling the alarm","volume":"129","author":"F Roan","year":"2019","journal-title":"The Journal of clinical investigation"},{"key":"ppat.1009905.ref028","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev.micro.60.080805.142126","article-title":"Francisella tularensis: taxonomy, genetics, and Immunopathogenesis of a potential agent of biowarfare","volume":"60","author":"MK McLendon","year":"2006","journal-title":"Annu Rev Microbiol"},{"key":"ppat.1009905.ref029","article-title":"Innate immune response to Francisella tularensis is mediated by TLR2 and caspase-1 activation","author":"H Li","year":"2006","journal-title":"Journal of leukocyte biology"},{"issue":"7","key":"ppat.1009905.ref030","doi-asserted-by":"crossref","first-page":"3751","DOI":"10.1074\/jbc.M706854200","article-title":"Identification of Francisella tularensis lipoproteins that stimulate the toll-like receptor (TLR) 2\/TLR1 heterodimer","volume":"283","author":"S Thakran","year":"2008","journal-title":"J Biol Chem"},{"issue":"5","key":"ppat.1009905.ref031","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1128\/IAI.74.5.2809-2816.2006","article-title":"Toll-like receptor 2 is required for inflammatory responses to Francisella tularensis LVS","volume":"74","author":"J Katz","year":"2006","journal-title":"Infect Immun"},{"issue":"6","key":"ppat.1009905.ref032","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1128\/IAI.02030-05","article-title":"Toll-like receptor 2 is required for control of pulmonary infection with Francisella tularensis","volume":"74","author":"M Malik","year":"2006","journal-title":"Infect Immun"},{"issue":"11","key":"ppat.1009905.ref033","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1111\/j.1462-5822.2007.01022.x","article-title":"Activation of the inflammasome upon Francisella tularensis infection: interplay of innate immune pathways and virulence factors","volume":"9","author":"T Henry","year":"2007","journal-title":"Cell Microbiol"},{"issue":"6","key":"ppat.1009905.ref034","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1128\/iai.64.6.2041-2046.1996","article-title":"Inability of the Francisella tularensis lipopolysaccharide to mimic or to antagonize the induction of cell activation by endotoxins","volume":"64","author":"P Ancuta","year":"1996","journal-title":"Infect Immun"},{"issue":"12","key":"ppat.1009905.ref035","doi-asserted-by":"crossref","first-page":"6730","DOI":"10.1128\/IAI.00934-06","article-title":"Lack of in vitro and in vivo recognition of Francisella tularensis subspecies lipopolysaccharide by Toll-like receptors","volume":"74","author":"AM Hajjar","year":"2006","journal-title":"Infect Immun"},{"issue":"6","key":"ppat.1009905.ref036","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.1128\/IAI.02011-05","article-title":"Basis for the failure of Francisella tularensis lipopolysaccharide to prime human polymorphonuclear leukocytes","volume":"74","author":"JH Barker","year":"2006","journal-title":"Infect Immun"},{"key":"ppat.1009905.ref037","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/j.1600-065X.2008.00689.x","article-title":"Humoral and cell-mediated immunity to the intracellular pathogen Francisella tularensis","volume":"225","author":"GS Kirimanjeswara","year":"2008","journal-title":"Immunological reviews"},{"key":"ppat.1009905.ref038","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1196\/annals.1409.014","article-title":"Innate and adaptive immunity to Francisella","volume":"1105","author":"KL Elkins","year":"2007","journal-title":"Ann N Y Acad Sci"},{"issue":"4","key":"ppat.1009905.ref039","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1128\/IAI.68.4.1988-1996.2000","article-title":"Purified lipopolysaccharide from Francisella tularensis live vaccine strain (LVS) induces protective immunity against LVS infection that requires B cells and gamma interferon","volume":"68","author":"VC Dreisbach","year":"2000","journal-title":"Infect Immun"},{"issue":"11","key":"ppat.1009905.ref040","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1084\/jem.20061041","article-title":"Regulation of B1 cell migration by signals through Toll-like receptors","volume":"203","author":"SA Ha","year":"2006","journal-title":"The Journal of experimental medicine"},{"issue":"9","key":"ppat.1009905.ref041","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1084\/jem.20161122","article-title":"Blimp-1-dependent and -independent natural antibody production by B-1 and B-1-derived plasma cells","volume":"214","author":"HP Savage","year":"2017","journal-title":"The Journal of experimental medicine"},{"issue":"1","key":"ppat.1009905.ref042","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1093\/intimm\/1.1.75","article-title":"Many of the IgA producing plasma cells in murine gut are derived from self-replenishing precursors in the peritoneal cavity","volume":"1","author":"FG Kroese","year":"1989","journal-title":"International immunology"},{"issue":"1","key":"ppat.1009905.ref043","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.immuni.2005.07.001","article-title":"Divide and conquer: division of labor by B-1 B cells","volume":"23","author":"KR Alugupalli","year":"2005","journal-title":"Immunity"},{"issue":"9","key":"ppat.1009905.ref044","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.4049\/jimmunol.1901453","article-title":"B Cell Subsets Differentially Contribute to the T Cell-Independent Memory Pool","volume":"205","author":"CA Daly","year":"2020","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"issue":"11","key":"ppat.1009905.ref045","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1002\/eji.1830251110","article-title":"Administration of interleukin-5 or -10 activates peritoneal B-1 cells and induces autoimmune hemolytic anemia in anti-erythrocyte autoantibody-transgenic mice","volume":"25","author":"S Nisitani","year":"1995","journal-title":"European journal of immunology"},{"issue":"5","key":"ppat.1009905.ref046","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S1074-7613(00)80414-8","article-title":"Defective B-1 cell development and impaired immunity against Angiostrongylus cantonensis in IL-5R alpha-deficient mice","volume":"4","author":"T Yoshida","year":"1996","journal-title":"Immunity"},{"issue":"10","key":"ppat.1009905.ref047","doi-asserted-by":"crossref","first-page":"6020","DOI":"10.4049\/jimmunol.172.10.6020","article-title":"The role of IL-5 for mature B-1 cells in homeostatic proliferation, cell survival, and Ig production","volume":"172","author":"BG Moon","year":"2004","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"issue":"10","key":"ppat.1009905.ref048","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1093\/intimm\/2.10.965","article-title":"In vivo expression of interleukin 5 induces an eosinophilia and expanded Ly-1B lineage populations","volume":"2","author":"DL Vaux","year":"1990","journal-title":"International immunology"},{"issue":"7470","key":"ppat.1009905.ref049","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nature12526","article-title":"Type 2 innate lymphoid cells control eosinophil homeostasis","volume":"502","author":"JC Nussbaum","year":"2013","journal-title":"Nature"},{"issue":"6371","key":"ppat.1009905.ref050","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1126\/science.aam5809","article-title":"S1P-dependent interorgan trafficking of group 2 innate lymphoid cells supports host defense","volume":"359","author":"Y Huang","year":"2018","journal-title":"Science (New York, NY)"},{"issue":"6972","key":"ppat.1009905.ref051","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature02284","article-title":"Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1","volume":"427","author":"M Matloubian","year":"2004","journal-title":"Nature"},{"issue":"2","key":"ppat.1009905.ref052","doi-asserted-by":"crossref","first-page":"e1001255","DOI":"10.1371\/journal.pbio.1001255","article-title":"Development and function of invariant natural killer T cells producing T(h)2- and T(h)17-cytokines","volume":"10","author":"H Watarai","year":"2012","journal-title":"PLoS biology"},{"key":"ppat.1009905.ref053","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.coi.2019.01.003","article-title":"What B cell memories are made of","volume":"57","author":"MM Tomayko","year":"2019","journal-title":"Current opinion in immunology"},{"issue":"6","key":"ppat.1009905.ref054","article-title":"Protection against Staphylococcus aureus bacteremia-induced mortality depends on ILC2s and eosinophils","volume":"4","author":"PA Krishack","year":"2019","journal-title":"JCI insight"},{"issue":"7280","key":"ppat.1009905.ref055","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nature08636","article-title":"Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells","volume":"463","author":"K Moro","year":"2010","journal-title":"Nature"},{"issue":"4","key":"ppat.1009905.ref056","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.4049\/jimmunol.1502669","article-title":"Group 2 Innate Lymphoid Cells Promote an Early Antibody Response to a Respiratory Antigen in Mice","volume":"197","author":"LY Drake","year":"2016","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"issue":"9","key":"ppat.1009905.ref057","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/s41577-019-0176-x","article-title":"Regulation of immune responses by tuft cells","volume":"19","author":"C Schneider","year":"2019","journal-title":"Nature reviews Immunology"},{"key":"ppat.1009905.ref058","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1034\/j.1600-065X.2000.00607.x","article-title":"B-cell activation by T-cell-independent type 2 antigens as an integral part of the humoral immune response to pathogenic microorganisms","volume":"176","author":"Q Vos","year":"2000","journal-title":"Immunological reviews"},{"issue":"15","key":"ppat.1009905.ref059","doi-asserted-by":"crossref","first-page":"5905","DOI":"10.1073\/pnas.0601502103","article-title":"B cell clones that sustain long-term plasmablast growth in T-independent extrafollicular antibody responses","volume":"103","author":"MC Hsu","year":"2006","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"6","key":"ppat.1009905.ref060","doi-asserted-by":"crossref","first-page":"3740","DOI":"10.4049\/jimmunol.178.6.3740","article-title":"MyD88- and Bruton\u2019s tyrosine kinase-mediated signals are essential for T cell-independent pathogen-specific IgM responses","volume":"178","author":"KR Alugupalli","year":"2007","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"issue":"4","key":"ppat.1009905.ref061","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/imm.12093","article-title":"Salmonella Typhi OmpS1 and OmpS2 porins are potent protective immunogens with adjuvant properties","volume":"139","author":"MA Moreno-Eutimio","year":"2013","journal-title":"Immunology"},{"key":"ppat.1009905.ref062","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.46997","article-title":"TLR induces reorganization of the IgM-BCR complex regulating murine B-1 cell responses to infections","volume":"8","author":"HP Savage","year":"2019","journal-title":"eLife"},{"issue":"5","key":"ppat.1009905.ref063","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.4049\/jimmunol.175.5.3084","article-title":"In vivo humoral immune responses to isolated pneumococcal polysaccharides are dependent on the presence of associated TLR ligands","volume":"175","author":"G Sen","year":"2005","journal-title":"Journal of immunology (Baltimore, Md: 1950)"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1009905","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T00:00:00Z","timestamp":1631145600000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009905","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T18:26:27Z","timestamp":1631211987000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009905"}},"subtitle":[],"editor":[{"given":"Robert K.","family":"Ernst","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,8,27]]},"references-count":63,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1009905","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1009905","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,27]]}}}