{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T05:46:01Z","timestamp":1793079961372,"version":"4.5.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":280,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>To defend against intracellular pathogens such as Toxoplasma gondii, the host generates a robust type 1 immune response. Specifically, host defense against T. gondii is defined by an IL-12\u2013dependent IFN-\u03b3 response that is critical for host resistance. Previously, we demonstrated that host resistance is mediated by T-bet\u2013dependent ILC-derived IFN-\u03b3 by maintaining IRF8+ conventional type 1 dendritic cells during parasitic infection. Therefore, we hypothesized that innate lymphoid cells are indispensable for host survival. Surprisingly, we observed that T-bet\u2013deficient mice succumb to infection quicker than do mice lacking lymphocytes, suggesting an unknown T-bet-dependent\u2013mediated host defense pathway. Analysis of parasite-mediated inflammatory myeloid cells revealed a novel subpopulation of T-bet+ myeloid cells (TMCs). Our results reveal that TMCs have the largest intracellular parasite burden compared with other professional phagocytes, suggesting they are associated with active killing of T. gondii. Mechanistically, we established that IL-12 is necessary for the induction of inflammatory TMCs during infection and these cells are linked to a role in host survival.<\/jats:p>","DOI":"10.4049\/immunohorizons.2400029","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T13:31:54Z","timestamp":1714483914000},"page":"355-362","source":"Crossref","is-referenced-by-count":5,"title":["IL-12 Mediates T-bet\u2013Expressing Myeloid Cell\u2013Dependent Host Resistance against <i>Toxoplasma gondii<\/i>"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8696-4430","authenticated-orcid":false,"given":"Madison L","family":"Schanz","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine\u2013Terre Haute , Terre Haute, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5710-3452","authenticated-orcid":false,"given":"Abigail M","family":"Bitters","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine\u2013Terre Haute , Terre Haute, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5763-5807","authenticated-orcid":false,"given":"Kamryn E","family":"Zadeii","sequence":"additional","affiliation":[{"name":"Department of Biology, Indiana State University , Terre Haute, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2181-9502","authenticated-orcid":false,"given":"Dana","family":"Joulani","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine\u2013Terre Haute , Terre Haute, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela K","family":"Chamberlain","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine\u2013Terre Haute , Terre Haute, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6797-2179","authenticated-orcid":false,"given":"Am\u00e9rico H","family":"L\u00f3pez-Yglesias","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine\u2013Terre Haute , Terre Haute, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"2025010608551754900_r1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nri3598","article-title":"Innate immunity to Toxoplasma gondii infection","volume":"14","author":"Yarovinsky","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"2025010608551754900_r2","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/s41577-019-0145-4","article-title":"The evolving role of T-bet in resistance to infection","volume":"19","author":"Pritchard","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"2025010608551754900_r3","doi-asserted-by":"crossref","first-page":"286","DOI":"10.4049\/jimmunol.146.1.286","article-title":"Synergistic role of CD4+ and CD8+ T lymphocytes in IFN-gamma production and protective immunity induced by an attenuated Toxoplasma gondii vaccine","volume":"146","author":"Gazzinelli","year":"1991","journal-title":"J. Immunol."},{"key":"2025010608551754900_r4","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1126\/science.3128869","article-title":"Interferon-\u03b3: the major mediator of resistance against Toxoplasma gondii","volume":"240","author":"Suzuki","year":"1988","journal-title":"Science"},{"key":"2025010608551754900_r5","doi-asserted-by":"crossref","first-page":"5997","DOI":"10.4049\/jimmunol.168.12.5997","article-title":"Cutting edge: MyD88 is required for resistance to Toxoplasma gondii infection and regulates parasite-induced IL-12 production by dendritic cells","volume":"168","author":"Scanga","year":"2002","journal-title":"J. Immunol."},{"key":"2025010608551754900_r6","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1073\/pnas.1011549108","article-title":"Critical coordination of innate immune defense against Toxoplasma gondii by dendritic cells responding via their Toll-like receptors","volume":"108","author":"Hou","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025010608551754900_r7","doi-asserted-by":"crossref","first-page":"e1008299","DOI":"10.1371\/journal.ppat.1008299","article-title":"T-bet-dependent ILC1- and NK cell-derived IFN-\u03b3 mediates cDC1-dependent host resistance against Toxoplasma gondii","volume":"17","author":"L\u00f3pez-Yglesias","year":"2021","journal-title":"PLoS Pathog."},{"key":"2025010608551754900_r8","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.immuni.2012.03.026","article-title":"NK cell-derived interferon-\u03b3 orchestrates cellular dynamics and the differentiation of monocytes into dendritic cells at the site of infection","volume":"36","author":"Goldszmid","year":"2012","journal-title":"Immunity"},{"key":"2025010608551754900_r9","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/j.immuni.2015.05.011","article-title":"Bone-marrow-resident NK cells prime monocytes for regulatory function during infection","volume":"42","author":"Askenase","year":"2015","journal-title":"Immunity"},{"key":"2025010608551754900_r10","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.cell.2014.03.030","article-title":"Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages","volume":"157","author":"Klose","year":"2014","journal-title":"Cell"},{"key":"2025010608551754900_r11","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1084\/jem.194.2.181","article-title":"Inactivation of LRG-47 and IRG-47 reveals a family of interferon \u03b3-inducible genes with essential, pathogen-specific roles in resistance to infection","volume":"194","author":"Collazo","year":"2001","journal-title":"J. Exp. Med."},{"key":"2025010608551754900_r12","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.immuni.2012.06.009","article-title":"A cluster of interferon-\u03b3-inducible p65 GTPases plays a critical role in host defense against Toxoplasma gondii","volume":"37","author":"Yamamoto","year":"2012","journal-title":"Immunity"},{"key":"2025010608551754900_r13","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1073\/pnas.1205635110","article-title":"Murine guanylate binding protein 2 (mGBP2) controls Toxoplasma gondii replication","volume":"110","author":"Degrandi","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025010608551754900_r14","doi-asserted-by":"crossref","first-page":"5209","DOI":"10.1038\/s41598-017-05487-7","article-title":"TRIM21 is critical for survival of Toxoplasma gondii infection and localises to GBP-positive parasite vacuoles","volume":"7","author":"Foltz","year":"2017","journal-title":"Sci. Rep."},{"key":"2025010608551754900_r15","doi-asserted-by":"crossref","first-page":"e1005619","DOI":"10.1371\/journal.pgen.1005619","article-title":"Transcriptional and linkage analyses identify loci that mediate the differential macrophage response to inflammatory stimuli and infection","volume":"11","author":"Hassan","year":"2015","journal-title":"PLoS Genet."},{"key":"2025010608551754900_r16","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.4049\/jimmunol.1401617","article-title":"Diverse roles for T-bet in the effector responses required for resistance to infection","volume":"194","author":"Harms Pritchard","year":"2015","journal-title":"J. Immunol."},{"key":"2025010608551754900_r17","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/mi.2017.102","article-title":"T-bet-independent Th1 response induces intestinal immunopathology during Toxoplasma gondii infection","volume":"11","author":"L\u00f3pez-Yglesias","year":"2018","journal-title":"Mucosal. Immunol."},{"key":"2025010608551754900_r18","doi-asserted-by":"crossref","first-page":"e1007872","DOI":"10.1371\/journal.ppat.1007872","article-title":"TLR11-independent inflammasome activation is critical for CD4+ T cell-derived IFN-\u03b3 production and host resistance to Toxoplasma gondii","volume":"15","author":"Lopez-Yglesias","year":"2019","journal-title":"PLoS Pathog."},{"key":"2025010608551754900_r19","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.immuni.2017.05.005","article-title":"The transcription factor T-bet limits amplification of type I IFN transcriptome and circuitry in T helper 1 cells","volume":"46","author":"Iwata","year":"2017","journal-title":"Immunity"},{"key":"2025010608551754900_r20","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S0092-8674(00)80702-3","article-title":"A novel transcription factor, T-bet, directs Th1 lineage commitment","volume":"100","author":"Szabo","year":"2000","journal-title":"Cell"},{"key":"2025010608551754900_r21","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1126\/science.1065543","article-title":"Distinct effects of T-bet in TH1 lineage commitment and IFN-\u03b3 production in CD4 and CD8 T cells","volume":"295","author":"Szabo","year":"2002","journal-title":"Science"},{"key":"2025010608551754900_r22","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1084\/jem.186.9.1523","article-title":"Interferon consensus sequence binding protein-deficient mice display impaired resistance to intracellular infection due to a primary defect in interleukin 12 p40 induction","volume":"186","author":"Scharton-Kersten","year":"1997","journal-title":"J. Exp. Med."},{"key":"2025010608551754900_r23","doi-asserted-by":"crossref","first-page":"4818","DOI":"10.4049\/jimmunol.1301301","article-title":"Cooperation of TLR12 and TLR11 in the IRF8-dependent IL-12 response to Toxoplasma gondii profilin","volume":"191","author":"Raetz","year":"2013","journal-title":"J. Immunol."},{"key":"2025010608551754900_r24","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.cell.2007.08.017","article-title":"Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system","volume":"131","author":"Garrett","year":"2007","journal-title":"Cell"},{"key":"2025010608551754900_r25","doi-asserted-by":"crossref","first-page":"13248","DOI":"10.1073\/pnas.0506638102","article-title":"The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells","volume":"102","author":"Lugo-Villarino","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025010608551754900_r26","doi-asserted-by":"crossref","first-page":"7749","DOI":"10.1073\/pnas.1332767100","article-title":"T-bet is required for optimal production of IFN-\u03b3 and antigen-specific T cell activation by dendritic cells","volume":"100","author":"Lugo-Villarino","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025010608551754900_r27","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1172\/JCI26631","article-title":"Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells","volume":"116","author":"Wang","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2025010608551754900_r28","doi-asserted-by":"crossref","first-page":"15137","DOI":"10.1073\/pnas.261570598","article-title":"T-bet is rapidly induced by interferon-\u03b3 in lymphoid and myeloid cells","volume":"98","author":"Lighvani","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025010608551754900_r29","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1128\/IAI.00472-09","article-title":"Inflammatory monocytes but not neutrophils are necessary to control infection with Toxoplasma gondii in mice","volume":"78","author":"Dunay","year":"2010","journal-title":"Infect. Immun."},{"key":"2025010608551754900_r30","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.4049\/jimmunol.1402037","article-title":"Ly6Chigh monocytes control cerebral toxoplasmosis","volume":"194","author":"Biswas","year":"2015","journal-title":"J. Immunol."},{"key":"2025010608551754900_r31","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S1074-7613(03)00171-7","article-title":"TNF\/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection","volume":"19","author":"Serbina","year":"2003","journal-title":"Immunity"},{"key":"2025010608551754900_r32","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1074-7613(03)00174-2","article-title":"Blood monocytes consist of two principal subsets with distinct migratory properties","volume":"19","author":"Geissmann","year":"2003","journal-title":"Immunity"},{"key":"2025010608551754900_r33","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/ni1340","article-title":"Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes","volume":"7","author":"Naik","year":"2006","journal-title":"Nat. Immunol."},{"key":"2025010608551754900_r34","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.immuni.2007.01.017","article-title":"Monocyte-derived dendritic cells formed at the infection site control the induction of protective T helper 1 responses against Leishmania","volume":"26","author":"Le\u00f3n","year":"2007","journal-title":"Immunity"},{"key":"2025010608551754900_r35","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1126\/science.1109893","article-title":"TLR11 activation of dendritic cells by a protozoan profilin-like protein","volume":"308","author":"Yarovinsky","year":"2005","journal-title":"Science"},{"key":"2025010608551754900_r36","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.cell.2017.09.052","article-title":"ILC1 confer early host protection at initial sites of viral infection","volume":"171","author":"Weizman","year":"2017","journal-title":"Cell"},{"key":"2025010608551754900_r37","doi-asserted-by":"crossref","first-page":"10711","DOI":"10.1073\/pnas.1307868110","article-title":"TLR-independent neutrophil-derived IFN-\u03b3 is important for host resistance to intracellular pathogens","volume":"110","author":"Sturge","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025010608551754900_r38","doi-asserted-by":"crossref","first-page":"36","DOI":"10.4049\/jimmunol.1500366","article-title":"Cutting edge: developmental regulation of IFN-\u03b3 production by mouse neutrophil precursor cells","volume":"195","author":"Sturge","year":"2015","journal-title":"J. Immunol."},{"key":"2025010608551754900_r39","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1073\/pnas.97.2.751","article-title":"Pathogen-specific loss of host resistance in mice lacking the IFN-\u03b3-inducible gene IGTP","volume":"97","author":"Taylor","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025010608551754900_r40","doi-asserted-by":"crossref","first-page":"3328","DOI":"10.4049\/jimmunol.1302822","article-title":"Role of mouse and human autophagy proteins in IFN-\u03b3-induced cell-autonomous responses against Toxoplasma gondii","volume":"192","author":"Ohshima","year":"2014","journal-title":"J. Immunol."},{"key":"2025010608551754900_r41","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1073\/pnas.81.3.908","article-title":"Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan","volume":"81","author":"Pfefferkorn","year":"1984","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025010608551754900_r42","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1089\/jir.1986.6.267","article-title":"Characterization of an indoleamine 2,3-dioxygenase induced by gamma-interferon in cultured human fibroblasts","volume":"6","author":"Pfefferkorn","year":"1986","journal-title":"J. Interferon. Res."},{"key":"2025010608551754900_r43","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.4049\/jimmunol.144.7.2725","article-title":"Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii. Role for synthesis of inorganic nitrogen oxides from l-arginine","volume":"144","author":"Adams","year":"1990","journal-title":"J. Immunol."},{"key":"2025010608551754900_r44","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.ijpara.2003.12.001","article-title":"Toxoplasma gondii lacks the enzymes required for de novo arginine biosynthesis and arginine starvation triggers cyst formation","volume":"34","author":"Fox","year":"2004","journal-title":"Int. J. Parasitol."},{"key":"2025010608551754900_r45","doi-asserted-by":"crossref","first-page":"e1002236","DOI":"10.1371\/journal.ppat.1002236","article-title":"Toxoplasma gondii rhoptry kinase ROP16 activates STAT3 and STAT6 resulting in cytokine inhibition and arginase-1-dependent growth control","volume":"7","author":"Butcher","year":"2011","journal-title":"PLoS Pathog."},{"key":"2025010608551754900_r46","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1038\/ni.1671","article-title":"Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens","volume":"9","author":"El Kasmi","year":"2008","journal-title":"Nat. Immunol."}],"container-title":["ImmunoHorizons"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/immunohorizons\/article-pdf\/8\/4\/355\/60188693\/ih2400029.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/immunohorizons\/article-pdf\/8\/4\/355\/60188693\/ih2400029.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T08:56:45Z","timestamp":1736153805000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/immunohorizons\/article\/8\/4\/355\/7816991"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,1]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4,1]]}},"URL":"https:\/\/doi.org\/10.4049\/immunohorizons.2400029","relation":{},"ISSN":["2573-7732"],"issn-type":[{"value":"2573-7732","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,4]]},"published":{"date-parts":[[2024,4,1]]}}}