{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T01:31:41Z","timestamp":1779154301525,"version":"3.51.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000032","name":"Gouvernement du Canada | CIHR | Institute of Infection and Immunity","doi-asserted-by":"publisher","award":["388337"],"award-info":[{"award-number":["388337"]}],"id":[{"id":"10.13039\/501100000032","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2019-04521"],"award-info":[{"award-number":["RGPIN-2019-04521"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Commensal intestinal protozoa, unlike their pathogenic relatives, are neglected members of the mammalian microbiome. These microbes have a significant impact on the host\u2019s intestinal immune homeostasis, typically by elevating anti-microbial host defense. Tritrichomonas musculis, a protozoan gut commensal, strengthens the intestinal host defense against enteric Salmonella infections through Asc- and Il1r1-dependent Th1 and Th17 cell activation. However, the underlying inflammasomes mediating this effect remain unknown. In this study, we report that colonization with T. musculis results in an increase in luminal extracellular ATP that is followed by increased caspase activity, higher cell death, elevated levels of IL-1\u03b2, and increased numbers of IL-18 receptor\u2013expressing Th1 and Th17 cells in the colon. Mice deficient in either Nlrp1b or Nlrp3 failed to display these protozoan-driven immune changes and lost resistance to enteric Salmonella infections even in the presence of T. musculis. These findings demonstrate that T. musculis\u2013mediated host protection requires sensors of extracellular and intracellular ATP to confer resistance to enteric Salmonella infections.<\/jats:p>","DOI":"10.4049\/jimmunol.2100802","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T12:25:14Z","timestamp":1646655914000},"page":"1782-1789","source":"Crossref","is-referenced-by-count":29,"title":["NLRP1B and NLRP3 Control the Host Response following Colonization with the Commensal Protist\n                    <i>Tritrichomonas musculis<\/i>"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8753-1469","authenticated-orcid":false,"given":"Pailin","family":"Chiaranunt","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-3512","authenticated-orcid":false,"given":"Kyle","family":"Burrows","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis","family":"Ngai","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric Y","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siu Ling","family":"Tai","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine J","family":"Streutker","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto , Toronto, Ontario,","place":["Canada"]},{"name":"Saint Michael\u2019s Hospital , Toronto, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9208-8879","authenticated-orcid":false,"given":"Stephen E","family":"Girardin","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario,","place":["Canada"]},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto , Toronto, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2673-0485","authenticated-orcid":false,"given":"Arthur","family":"Mortha","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,4,1]]},"reference":[{"key":"2025021009003259800_r1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.ebiom.2016.10.007","article-title":"The multibiome: the intestinal ecosystem\u2019s influence on immune homeostasis, health, and disease","volume":"13","author":"Filyk","year":"2016","journal-title":"EBioMedicine"},{"key":"2025021009003259800_r2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.mib.2021.04.004","article-title":"The intestinal mycobiome as a determinant of host immune and metabolic health","volume":"62","author":"Gutierrez","year":"2021","journal-title":"Curr. Opin. Microbiol."},{"key":"2025021009003259800_r3","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.chom.2020.03.006","article-title":"Fungal trans-kingdom dynamics linked to responsiveness to fecal microbiota transplantation (FMT) therapy in ulcerative colitis","volume":"27","author":"Leonardi","year":"2020","journal-title":"Cell Host Microbe"},{"key":"2025021009003259800_r4","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.cell.2021.01.016","article-title":"Human gut mycobiota tune immunity via CARD9-dependent induction of anti-fungal IgG antibodies","volume":"184","author":"Doron","year":"2021","journal-title":"Cell"},{"key":"2025021009003259800_r5","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41586-021-03722-w","article-title":"Adaptive immunity induces mutualism between commensal eukaryotes","volume":"596","author":"Ost","year":"2021","journal-title":"Nature"},{"key":"2025021009003259800_r6","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1016\/j.chom.2021.03.015","article-title":"Enteric viruses evoke broad host immune responses resembling those elicited by the bacterial microbiome","volume":"29","author":"Dallari","year":"2021","journal-title":"Cell Host Microbe"},{"key":"2025021009003259800_r7","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.chom.2020.02.015","article-title":"Altered immunity of laboratory mice in the natural environment is associated with fungal colonization","volume":"27","author":"Yeung","year":"2020","journal-title":"Cell Host Microbe"},{"key":"2025021009003259800_r8","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1146\/annurev-physiol-020911-153330","article-title":"Toll-like receptor-gut microbiota interactions: perturb at your own risk!","volume":"74","author":"Carvalho","year":"2012","journal-title":"Annu. Rev. Physiol."},{"key":"2025021009003259800_r9","doi-asserted-by":"crossref","first-page":"R171","DOI":"10.1016\/j.cub.2008.12.027","article-title":"Gut Immunity: a NOD to the commensals","volume":"19","author":"Chen","year":"2009","journal-title":"Curr. Biol."},{"key":"2025021009003259800_r10","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1093\/intimm\/dxp017","article-title":"The roles of TLRs, RLRs and NLRs in pathogen recognition","volume":"21","author":"Kawai","year":"2009","journal-title":"Int. Immunol."},{"key":"2025021009003259800_r11","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2018.05.014","article-title":"A metabolite-triggered tuft cell-ILC2 circuit drives small intestinal remodeling","volume":"174","author":"Schneider","year":"2018","journal-title":"Cell"},{"key":"2025021009003259800_r12","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.immuni.2018.06.016","article-title":"Detection of succinate by intestinal tuft cells triggers a type 2 innate immune circuit","volume":"49","author":"Nadjsombati","year":"2018","journal-title":"Immunity"},{"key":"2025021009003259800_r13","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1128\/CMR.05038-11","article-title":"Enteric protozoa in the developed world: a public health perspective","volume":"25","author":"Fletcher","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"2025021009003259800_r14","doi-asserted-by":"crossref","first-page":"e1005039","DOI":"10.1371\/journal.ppat.1005039","article-title":"Are human intestinal eukaryotes beneficial or commensals?","volume":"11","author":"Luke\u0161","year":"2015","journal-title":"PLoS Pathog."},{"key":"2025021009003259800_r15","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/pch\/3.2.81","article-title":"Dientamoeba fragilis: a harmless commensal or a mild pathogen?","volume":"3","year":"1998","journal-title":"Paediatr. Child Health"},{"key":"2025021009003259800_r16","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1084\/jem.20161776","article-title":"The common mouse protozoa Tritrichomonas muris alters mucosal T cell homeostasis and colitis susceptibility","volume":"213","author":"Escalante","year":"2016","journal-title":"J. Exp. Med."},{"key":"2025021009003259800_r17","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.cell.2016.08.076","article-title":"Host-protozoan interactions protect from mucosal infections through activation of the inflammasome","volume":"167","author":"Chudnovskiy","year":"2016","journal-title":"Cell"},{"key":"2025021009003259800_r18","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1126\/science.aaf1648","article-title":"Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut","volume":"351","author":"Howitt","year":"2016","journal-title":"Science"},{"key":"2025021009003259800_r19","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/bs.mie.2019.10.004","article-title":"Isolation of mononuclear phagocytes from the mouse gut","volume":"632","author":"Chiaranunt","year":"2020","journal-title":"Methods Enzymol."},{"key":"2025021009003259800_r20","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.1128\/IAI.71.5.2839-2858.2003","article-title":"Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host","volume":"71","author":"Barthel","year":"2003","journal-title":"Infect. Immun."},{"key":"2025021009003259800_r21","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/nature13085","article-title":"Nucleotide signalling during inflammation","volume":"509","author":"Idzko","year":"2014","journal-title":"Nature"},{"key":"2025021009003259800_r22","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1038\/nature07240","article-title":"ATP drives lamina propria TH17 cell differentiation","volume":"455","author":"Atarashi","year":"2008","journal-title":"Nature"},{"key":"2025021009003259800_r23","doi-asserted-by":"crossref","first-page":"4375","DOI":"10.4049\/jimmunol.1003020","article-title":"The danger signal, extracellular ATP, is a sensor for an airborne allergen and triggers IL-33 release and innate Th2-type responses","volume":"186","author":"Kouzaki","year":"2011","journal-title":"J. Immunol."},{"key":"2025021009003259800_r24","doi-asserted-by":"crossref","first-page":"4056","DOI":"10.1073\/pnas.1418549112","article-title":"T-bet- and STAT4-dependent IL-33 receptor expression directly promotes antiviral Th1 cell responses","volume":"112","author":"Baumann","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021009003259800_r25","doi-asserted-by":"crossref","first-page":"522","DOI":"10.3389\/fimmu.2019.00522","article-title":"Pleiotropic effects of IL-33 on CD4+ T cell differentiation and effector functions","volume":"10","author":"Alvarez","year":"2019","journal-title":"Front. Immunol."},{"key":"2025021009003259800_r26","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s10753-006-8967-1","article-title":"IL-18 receptor expression on epithelial cells is upregulated by TNF alpha","volume":"29","author":"Kr\u00e1sn\u00e1","year":"2005","journal-title":"Inflammation"},{"key":"2025021009003259800_r27","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1038\/sj.leu.2401789","article-title":"Expression and responsiveness of human interleukin-18 receptor (IL-18R) on hematopoietic cell lines","volume":"14","author":"Nakamura","year":"2000","journal-title":"Leukemia"},{"key":"2025021009003259800_r28","doi-asserted-by":"crossref","first-page":"e01117-13","DOI":"10.1128\/mBio.01117-13","article-title":"Dual role for inflammasome sensors NLRP1 and NLRP3 in murine resistance to Toxoplasma gondii","volume":"5","author":"Gorfu","year":"2014","journal-title":"MBio"},{"key":"2025021009003259800_r29","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.1128\/iai.62.7.2818-2824.1994","article-title":"Production of gamma interferon by natural killer cells from Toxoplasma gondii-infected SCID mice: regulation by interleukin-10, interleukin-12, and tumor necrosis factor alpha","volume":"62","author":"Hunter","year":"1994","journal-title":"Infect. Immun."},{"key":"2025021009003259800_r30","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1128\/IAI.01170-13","article-title":"NLRP1 is an inflammasome sensor for Toxoplasma gondii","volume":"82","author":"Ewald","year":"2014","journal-title":"Infect. Immun."},{"key":"2025021009003259800_r31","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1128\/IAI.01003-12","article-title":"Activation of the Nlrp1b inflammasome by reduction of cytosolic ATP","volume":"81","author":"Liao","year":"2013","journal-title":"Infect. Immun."},{"key":"2025021009003259800_r32","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/nature04515","article-title":"Cryopyrin activates the inflammasome in response to toxins and ATP","volume":"440","author":"Mariathasan","year":"2006","journal-title":"Nature"},{"key":"2025021009003259800_r33","doi-asserted-by":"crossref","first-page":"6242","DOI":"10.1128\/IAI.67.12.6242-6248.1999","article-title":"Role of endogenous interleukin-18 in resolving wild-type and attenuated Salmonella typhimurium infections","volume":"67","author":"Dybing","year":"1999","journal-title":"Infect. Immun."},{"key":"2025021009003259800_r34","doi-asserted-by":"crossref","first-page":"4922","DOI":"10.1128\/IAI.00417-06","article-title":"Caspase-1-mediated activation of interleukin-1\u03b2 (IL-1\u03b2) and IL-18 contributes to innate immune defenses against Salmonella enterica serovar Typhimurium infection","volume":"74","author":"Raupach","year":"2006","journal-title":"Infect. Immun."},{"key":"2025021009003259800_r35","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1186\/1471-2180-13-301","article-title":"Release of extracellular ATP by bacteria during growth","volume":"13","author":"Mempin","year":"2013","journal-title":"BMC Microbiol."},{"key":"2025021009003259800_r36","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1128\/CMR.00076-15","article-title":"Dientamoeba fragilis, the neglected trichomonad of the human bowel","volume":"29","author":"Stark","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"2025021009003259800_r37","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1086\/650733","article-title":"The global burden of nontyphoidal Salmonella gastroenteritis","volume":"50","author":"Majowicz","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"2025021009003259800_r38","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1186\/s12879-021-06340-z","article-title":"Characterization of Salmonella serotypes prevalent in asymptomatic people and patients","volume":"21","author":"Xu","year":"2021","journal-title":"BMC Infect. Dis."},{"key":"2025021009003259800_r39","doi-asserted-by":"crossref","first-page":"451","DOI":"10.3109\/00365549009027077","article-title":"Estimation of symptomatic and asymptomatic Salmonella infections","volume":"22","author":"Jertborn","year":"1990","journal-title":"Scand. J. Infect. Dis."},{"key":"2025021009003259800_r40","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1016\/j.celrep.2019.04.023","article-title":"Comparison of co-housing and littermate methods for microbiota standardization in mouse models","volume":"27","author":"Robertson","year":"2019","journal-title":"Cell Rep."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/208\/7\/1782\/61189968\/ji2100802.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/208\/7\/1782\/61189968\/ji2100802.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T04:00:51Z","timestamp":1739160051000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/208\/7\/1782\/7924540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,1]]},"references-count":40,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,4,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.2100802","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.08.14.455483","asserted-by":"object"}]},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,4]]},"published":{"date-parts":[[2022,4,1]]}}}