{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T13:10:42Z","timestamp":1781788242562,"version":"3.54.5"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":1588,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Leishmania spp. infection is a global health problem affecting more than 2 million people every year with 300 million at risk worldwide. It is well established that a dominant Th1 response (IFN-\u03b3, a hallmark Th1 cytokine) provides resistance, whereas a dominant Th2 response (IL-4, a hallmark Th2 cytokine) confers susceptibility during infection. Given the important role of IL-4 during L. major infection, we used IL-4\u2013neutralizing Abs to investigate the cellular and molecular events regulated by IL-4 signaling. As previously published, neutralization of IL-4 in L. major\u2013infected BALB\/c mice (a Leishmania susceptible strain) provided protection when compared with control L. major\u2013infected BALB\/c mice. Despite this protection, IFN-\u03b3 production by T cells was dramatically reduced. Temporal neutralization of IL-4 revealed that acute IL-4 produced within the first days of infection is critical for not only programming IL-4\u2013producing Th2 CD4+ T cells, but for promoting IFN-\u03b3 produced by CD8+ T cells. Mechanistically, IL-4 signaling enhances anti-CD3\u2013induced Tbet and IFN-\u03b3 expression in both CD4+ and CD8+ T cells. Given the pathogenic role of IFN-\u03b3\u2013producing CD8+ T cells, our data suggest that IL-4 promotes cutaneous leishmaniasis pathology by not only promoting Th2 immune responses but also pathogenic CD8+ T cell responses. Our studies open new research grounds to investigate the unsuspected role of IL-4 in regulating both Th1 and Th2 responses.<\/jats:p>","DOI":"10.4049\/immunohorizons.2000076","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T22:35:15Z","timestamp":1600468515000},"page":"546-560","source":"Crossref","is-referenced-by-count":17,"title":["Acute IL-4 Governs Pathogenic T Cell Responses during <i>Leishmania major<\/i> Infection"],"prefix":"10.1093","volume":"4","author":[{"given":"Barun","family":"Poudel","sequence":"first","affiliation":[{"name":"Iowa Inflammation Program, University of Iowa , Iowa City, IA 52242"},{"name":"Department of Internal Medicine, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4737-9367","authenticated-orcid":false,"given":"Matthew S","family":"Yorek","sequence":"additional","affiliation":[{"name":"Iowa Inflammation Program, University of Iowa , Iowa City, IA 52242"},{"name":"Department of Internal Medicine, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9467-3705","authenticated-orcid":false,"given":"Lalita","family":"Mazgaeen","sequence":"additional","affiliation":[{"name":"Iowa Inflammation Program, University of Iowa , Iowa City, IA 52242"},{"name":"Department of Internal Medicine, University of Iowa , Iowa City, IA 52242"},{"name":"Interdisciplinary Graduate Program in Human Toxicology, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6686-9695","authenticated-orcid":false,"given":"Scott A","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Immunology, St. Jude Children\u2019s Research Hospital , Memphis, TN 38105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6395-6443","authenticated-orcid":false,"given":"Thirumala-Devi","family":"Kanneganti","sequence":"additional","affiliation":[{"name":"Department of Immunology, St. Jude Children\u2019s Research Hospital , Memphis, TN 38105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7451-9433","authenticated-orcid":false,"given":"Prajwal","family":"Gurung","sequence":"additional","affiliation":[{"name":"Iowa Inflammation Program, University of Iowa , Iowa City, IA 52242"},{"name":"Department of Internal Medicine, University of Iowa , Iowa City, IA 52242"},{"name":"Interdisciplinary Graduate Program in Human Toxicology, University of Iowa , Iowa City, IA 52242"},{"name":"Immunology Graduate Program, University of Iowa , Iowa City, IA 52242"},{"name":"Center for Immunology and Immune Based Disease, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,21]]},"reference":[{"key":"2025010607445490600_r1","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nri933","article-title":"The immunology of susceptibility and resistance to Leishmania major in mice","volume":"2","author":"Sacks","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"2025010607445490600_r2","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/S0769-2625(87)80030-2","article-title":"Murine cutaneous leishmaniasis: susceptibility correlates with differential expansion of helper T-cell subsets","volume":"138","author":"Locksley","year":"1987","journal-title":"Ann. Inst. Pasteur Immunol."},{"key":"2025010607445490600_r3","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.4049\/jimmunol.139.4.1303","article-title":"Cellular and humoral immunity to Leishmania major in genetically susceptible mice after in vivo depletion of L3T4+ T cells","volume":"139","author":"Sadick","year":"1987","journal-title":"J. Immunol."},{"key":"2025010607445490600_r4","doi-asserted-by":"crossref","first-page":"896","DOI":"10.4049\/jimmunol.165.2.896","article-title":"IL-12 is required to maintain a Th1 response during Leishmania major infection","volume":"165","author":"Park","year":"2000","journal-title":"J. Immunol."},{"key":"2025010607445490600_r5","doi-asserted-by":"crossref","first-page":"5320","DOI":"10.4049\/jimmunol.154.10.5320","article-title":"IL-12 is required for natural killer cell activation and subsequent T helper 1 cell development in experimental leishmaniasis","volume":"154","author":"Scharton-Kersten","year":"1995","journal-title":"J. Immunol."},{"key":"2025010607445490600_r6","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1084\/jem.169.1.59","article-title":"Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets","volume":"169","author":"Heinzel","year":"1989","journal-title":"J. Exp. Med."},{"key":"2025010607445490600_r7","doi-asserted-by":"crossref","first-page":"7011","DOI":"10.1073\/pnas.88.16.7011","article-title":"Production of interferon gamma, interleukin 2, interleukin 4, and interleukin 10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis","volume":"88","author":"Heinzel","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025010607445490600_r8","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1172\/JCI111107","article-title":"Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-gamma is the activating lymphokine","volume":"72","author":"Murray","year":"1983","journal-title":"J. Clin. Invest."},{"key":"2025010607445490600_r9","doi-asserted-by":"crossref","first-page":"3062","DOI":"10.4049\/jimmunol.136.8.3062","article-title":"The enhancing effect of interferon-beta and -gamma on the killing of Leishmania tropica major in human mononuclear phagocytes in vitro","volume":"136","author":"Passwell","year":"1986","journal-title":"J. Immunol."},{"key":"2025010607445490600_r10","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1084\/jem.148.2.393","article-title":"Studies on the mechanisms of macrophage activation. I. Destruction of intracellular Leishmania enriettii in macrophages activated by cocultivation with stimulated lymphocytes","volume":"148","author":"Mauel","year":"1978","journal-title":"J. Exp. Med."},{"key":"2025010607445490600_r11","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1084\/jem.179.4.1367","article-title":"CD4+ effector cells default to the Th2 pathway in interferon gamma-deficient mice infected with Leishmania major","volume":"179","author":"Wang","year":"1994","journal-title":"J. Exp. Med."},{"key":"2025010607445490600_r12","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1084\/jem.181.3.961","article-title":"Mice from a genetically resistant background lacking the interferon gamma receptor are susceptible to infection with Leishmania major but mount a polarized T helper cell 1-type CD4+ T cell response","volume":"181","author":"Swihart","year":"1995","journal-title":"J. Exp. Med."},{"key":"2025010607445490600_r13","doi-asserted-by":"crossref","first-page":"266","DOI":"10.4049\/jimmunol.143.1.266","article-title":"Administration of monoclonal anti-IFN-gamma antibodies in vivo abrogates natural resistance of C3H\/HeN mice to infection with Leishmania major","volume":"143","author":"Belosevic","year":"1989","journal-title":"J. Immunol."},{"key":"2025010607445490600_r14","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1084\/jem.171.1.115","article-title":"Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon gamma-independent mechanism","volume":"171","author":"Sadick","year":"1990","journal-title":"J. Exp. Med."},{"key":"2025010607445490600_r15","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.chom.2020.03.011","article-title":"Th1-Th2 cross-regulation controls early leishmania infection in the skin by modulating the size of the permissive monocytic host cell reservoir","volume":"27","author":"Carneiro","year":"2020","journal-title":"Cell Host Microbe"},{"key":"2025010607445490600_r16","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.4049\/jimmunol.148.4.1182","article-title":"IL-4 induces a Th2 response in Leishmania major-infected mice","volume":"148","author":"Chatelain","year":"1992","journal-title":"J. Immunol."},{"key":"2025010607445490600_r17","doi-asserted-by":"crossref","first-page":"4710","DOI":"10.1128\/iai.59.12.4710-4714.1991","article-title":"Cytokine regulation of murine leishmaniasis: interleukin 4 is not sufficient to mediate progressive disease in resistant C57BL\/6 mice","volume":"59","author":"Sadick","year":"1991","journal-title":"Infect. 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Immunol."},{"key":"2025010607445490600_r21","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1084\/jem.20042463","article-title":"IL-4 receptor expression on CD8+ T cells is required for the development of protective memory responses against liver stages of malaria parasites","volume":"202","author":"Morrot","year":"2005","journal-title":"J. Exp. Med."},{"key":"2025010607445490600_r22","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1084\/jem.20151359","article-title":"IL-4 sensitivity shapes the peripheral CD8+ T cell pool and response to infection","volume":"213","author":"Renkema","year":"2016","journal-title":"J. Exp. Med."},{"key":"2025010607445490600_r23","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1084\/jem.187.3.307","article-title":"Endogenous interleukin 4 is required for development of protective CD4+ T helper type 1 cell responses to Candida albicans","volume":"187","author":"Mencacci","year":"1998","journal-title":"J. Exp. Med."},{"key":"2025010607445490600_r24","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/0092-8674(89)90925-2","article-title":"Murine interleukin-4 displays potent anti-tumor activity in vivo","volume":"57","author":"Tepper","year":"1989","journal-title":"Cell"},{"key":"2025010607445490600_r25","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/79811","article-title":"A critical role for interleukin 4 in activating alloreactive CD4 T cells","volume":"1","author":"Bagley","year":"2000","journal-title":"Nat. Immunol."},{"key":"2025010607445490600_r26","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1084\/jem.184.3.1127","article-title":"IL-4-deficient Balb\/c mice resist infection with Leishmania major","volume":"184","author":"Kopf","year":"1996","journal-title":"J. Exp. Med."},{"key":"2025010607445490600_r27","doi-asserted-by":"crossref","first-page":"7302","DOI":"10.4049\/jimmunol.162.12.7302","article-title":"Differences between IL-4- and IL-4 receptor alpha-deficient mice in chronic leishmaniasis reveal a protective role for IL-13 receptor signaling","volume":"162","author":"Mohrs","year":"1999","journal-title":"J. Immunol."},{"key":"2025010607445490600_r28","doi-asserted-by":"crossref","first-page":"6132","DOI":"10.4049\/jimmunol.162.10.6132","article-title":"IL-4- and IL-4 receptor-deficient BALB\/c mice reveal differences in susceptibility to Leishmania major parasite substrains","volume":"162","author":"Noben-Trauth","year":"1999","journal-title":"J. Immunol."},{"key":"2025010607445490600_r29","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1126\/science.271.5251.987","article-title":"Susceptibility to Leishmania major infection in interleukin-4-deficient mice","volume":"271","author":"Noben-Trauth","year":"1996","journal-title":"Science"},{"key":"2025010607445490600_r30","doi-asserted-by":"crossref","first-page":"3434","DOI":"10.4049\/jimmunol.159.7.3434","article-title":"Characterization of T cell-mediated responses in nonhealing and healing Leishmania major infections in the absence of endogenous IL-4","volume":"159","author":"Kropf","year":"1997","journal-title":"J. Immunol."},{"key":"2025010607445490600_r31","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/0923-2494(91)90007-6","article-title":"Induction of Th1 and Th2 CD4+ subsets during murine Leishmania major infection","volume":"142","author":"Locksley","year":"1991","journal-title":"Res. Immunol."},{"key":"2025010607445490600_r32","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003970","article-title":"Engagement of NKG2D on bystander memory CD8 T cells promotes increased immunopathology following Leishmania major infection","volume":"10","author":"Crosby","year":"2014","journal-title":"PLoS Pathog."},{"key":"2025010607445490600_r33","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1006196","article-title":"CD8+ T cell cytotoxicity mediates pathology in the skin by inflammasome activation and IL-1\u03b2 production","volume":"13","author":"Novais","year":"2017","journal-title":"PLoS Pathog."},{"key":"2025010607445490600_r34","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1172\/JCI79526","article-title":"An NLRP3 inflammasome-triggered Th2-biased adaptive immune response promotes leishmaniasis","volume":"125","author":"Gurung","year":"2015","journal-title":"J. Clin. Invest."},{"key":"2025010607445490600_r35","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/JLB.4HI0918-346R","article-title":"Frontline Science: Staphylococcus aureus promotes receptor-interacting protein kinase 3- and protease-dependent production of IL-1\u03b2 in human neutrophils","volume":"105","author":"Kremserova","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"2025010607445490600_r36","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1046\/j.1365-3024.1999.00240.x","article-title":"Leishmania major infection in interleukin-4 and interferon-gamma depleted mice","volume":"21","author":"Chatelain","year":"1999","journal-title":"Parasite Immunol."},{"key":"2025010607445490600_r37","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/j.1365-3024.2003.00655.x","article-title":"Factors influencing Leishmania major infection in IL-4-deficient BALB\/c mice","volume":"25","author":"Kropf","year":"2003","journal-title":"Parasite Immunol."},{"key":"2025010607445490600_r38","doi-asserted-by":"crossref","first-page":"5568","DOI":"10.4049\/jimmunol.1102104","article-title":"Quantifying antigen-specific CD4 T cells during a viral infection: CD4 T cell responses are larger than we think","volume":"187","author":"McDermott","year":"2011","journal-title":"J. Immunol."},{"key":"2025010607445490600_r39","doi-asserted-by":"crossref","first-page":"7672","DOI":"10.4049\/jimmunol.0902874","article-title":"Tracking the total CD8 T cell response to infection reveals substantial discordance in magnitude and kinetics between inbred and outbred hosts","volume":"183","author":"Rai","year":"2009","journal-title":"J. Immunol."},{"key":"2025010607445490600_r40","doi-asserted-by":"crossref","first-page":"3298","DOI":"10.1002\/eji.1830251215","article-title":"In susceptible mice, Leishmania major induce very rapid interleukin-4 production by CD4+ T cells which are NK1.1-","volume":"25","author":"Launois","year":"1995","journal-title":"Eur. J. Immunol."},{"key":"2025010607445490600_r41","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.4049\/jimmunol.158.7.3317","article-title":"Early production of IL-4 in susceptible mice infected with Leishmania major rapidly induces IL-12 unresponsiveness","volume":"158","author":"Launois","year":"1997","journal-title":"J. Immunol."},{"key":"2025010607445490600_r42","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S1074-7613(02)00363-1","article-title":"Rapid expansion and IL-4 expression by Leishmania-specific naive helper T cells in vivo","volume":"17","author":"Stetson","year":"2002","journal-title":"Immunity"},{"key":"2025010607445490600_r43","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S1074-7613(00)80342-8","article-title":"IL-4 rapidly produced by V beta 4 V alpha 8 CD4+ T cells instructs Th2 development and susceptibility to Leishmania major in BALB\/c mice","volume":"6","author":"Launois","year":"1997","journal-title":"Immunity"},{"key":"2025010607445490600_r44","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.4049\/jimmunol.165.5.2628","article-title":"An immunomodulatory function for neutrophils during the induction of a CD4+ Th2 response in BALB\/c mice infected with Leishmania major","volume":"165","author":"Tacchini-Cottier","year":"2000","journal-title":"J. Immunol."},{"key":"2025010607445490600_r45","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000871","article-title":"Keratinocytes determine Th1 immunity during early experimental leishmaniasis","volume":"6","author":"Ehrchen","year":"2010","journal-title":"PLoS Pathog."},{"key":"2025010607445490600_r46","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.3389\/fimmu.2017.01265","article-title":"IL-4R\u03b1 signaling in keratinocytes and early IL-4 production are dispensable for generating a curative T helper 1 response in Leishmania major-infected C57BL\/6 mice","volume":"8","author":"Descatoire","year":"2017","journal-title":"Front. Immunol."},{"key":"2025010607445490600_r47","doi-asserted-by":"crossref","first-page":"E8430","DOI":"10.1073\/pnas.1708125114","article-title":"IL-4-producing B cells regulate T helper cell dichotomy in type 1- and type 2-controlled diseases","volume":"114","author":"Hurdayal","year":"2017","journal-title":"Proc. Natl. Acad. Sci. 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Immunol."},{"key":"2025010607445490600_r51","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1084\/jem.20040172","article-title":"Low dose Leishmania major promotes a transient T helper cell type 2 response that is down-regulated by interferon gamma-producing CD8+ T cells","volume":"199","author":"Uzonna","year":"2004","journal-title":"J. Exp. Med."},{"key":"2025010607445490600_r52","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/eji.1830200528","article-title":"Tumor necrosis factor-alpha in combination with interferon-gamma, but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes","volume":"20","author":"Bogdan","year":"1990","journal-title":"Eur. J. Immunol."},{"key":"2025010607445490600_r53","first-page":"304","article-title":"TNF-alpha reverses the disease-exacerbating effect of subcutaneous immunization against murine cutaneous leishmaniasis","volume":"74","author":"Liew","year":"1991","journal-title":"Immunology"},{"key":"2025010607445490600_r54","doi-asserted-by":"crossref","first-page":"4012","DOI":"10.4049\/jimmunol.166.6.4012","article-title":"Rapidly fatal leishmaniasis in resistant C57BL\/6 mice lacking TNF","volume":"166","author":"Wilhelm","year":"2001","journal-title":"J. Immunol."},{"key":"2025010607445490600_r55","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.micinf.2004.02.008","article-title":"The control of Leishmania (Leishmania) major by TNF in vivo is dependent on the parasite strain","volume":"6","author":"Ritter","year":"2004","journal-title":"Microbes Infect."},{"key":"2025010607445490600_r56","doi-asserted-by":"crossref","first-page":"6289","DOI":"10.1128\/IAI.68.11.6289-6293.2000","article-title":"Visceral leishmaniasis in mice devoid of tumor necrosis factor and response to treatment","volume":"68","author":"Murray","year":"2000","journal-title":"Infect. Immun."},{"key":"2025010607445490600_r57","doi-asserted-by":"crossref","first-page":"827","DOI":"10.4049\/jimmunol.157.2.827","article-title":"Mice lacking the TNF receptor p55 fail to resolve lesions caused by infection with Leishmania major, but control parasite replication","volume":"157","author":"Vieira","year":"1996","journal-title":"J. Immunol."},{"key":"2025010607445490600_r58","doi-asserted-by":"crossref","first-page":"5506","DOI":"10.4049\/jimmunol.160.11.5506","article-title":"Control of Leishmania major infection in mice lacking TNF receptors","volume":"160","author":"Nashleanas","year":"1998","journal-title":"J. Immunol."},{"key":"2025010607445490600_r59","doi-asserted-by":"crossref","first-page":"3883","DOI":"10.4049\/jimmunol.163.7.3883","article-title":"TNF receptor p55 is required for elimination of inflammatory cells following control of intracellular pathogens","volume":"163","author":"Kanaly","year":"1999","journal-title":"J. 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