{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T08:40:21Z","timestamp":1775551221676,"version":"3.50.1"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T00:00:00Z","timestamp":1642118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>A variety of signaling pathways are involved in the induction of innate cytokines and CD8<jats:sup>+<\/jats:sup>T cells, which are major players in protection against acute<jats:italic>Trypanosoma cruzi<\/jats:italic>infection. Previous data have demonstrated that a TBK-1\/IRF3-dependent signaling pathway promotes IFN-\u03b2 production in response to<jats:italic>Trypanosoma cruzi<\/jats:italic>, but the role for STING, a main interactor of these proteins, remained to be addressed. Here, we demonstrated that STING signaling is required for production of IFN-\u03b2, IL-6, and IL-12 in response to<jats:italic>Trypanosoma cruzi<\/jats:italic>infection and that STING absence negatively impacts activation of IRF-dependent pathways in response to the parasite. We reported no significant activation of IRF-dependent pathways and cytokine expression in RAW264.7 macrophages in response to heat-killed trypomastigotes. In addition, we showed that STING is essential for<jats:italic>T. cruzi<\/jats:italic>DNA-mediated induction of IFN-\u03b2, IL-6, and IL-12 gene expression in RAW264.7 macrophages. We demonstrated that STING-knockout mice have significantly higher parasitemia from days 5 to 8 of infection and higher heart parasitism at day 13 after infection. Although we observed similar heart inflammatory infiltrates at day 13 after infection, IFN-\u03b2, IL-12, CXCL9, IFN-\u03b3, and perforin gene expression were lower in the absence of STING. We also showed an inverse correlation between parasite DNA and the expression of CXCL9, IFN-\u03b3, and perforin genes in the hearts of infected animals at day 13 after infection. Finally, we reported that\u00a0STING signaling is required for splenic IFN-\u03b2 and IL-6 expression early after infection and that STING deficiency results in lower numbers of splenic parasite-specific IFN-\u03b3 and IFN-\u03b3\/perforin-producing CD8<jats:sup>+<\/jats:sup>T cells, indicating a pivotal role for STING signaling in immunity to<jats:italic>Trypanosoma cruzi<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fimmu.2021.775346","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T05:44:51Z","timestamp":1642139091000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["STING Signaling Drives Production of Innate Cytokines, Generation of CD8+ T Cells and Enhanced Protection Against Trypanosoma cruzi Infection"],"prefix":"10.3389","volume":"12","author":[{"given":"Raquel de Souza","family":"Vieira","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilda Savoia","family":"Nascimento","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isa\u00fa Henrique","family":"Noronha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Ronnie Carvalho","family":"Vasconcelos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiz Alberto","family":"Benvenuti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glen N.","family":"Barber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels Olsen Saraiva","family":"C\u00e2mara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Kalil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edecio","family":"Cunha-Neto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael Ribeiro","family":"Almeida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(10)60061-x","article-title":"Chagas Disease","volume":"375","author":"Rassi","year":"2010","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02791","article-title":"Disease Tolerance and Pathogen Resistance Genes May Underlie Trypanosoma Cruzi Persistence and Differential Progression to Chagas Disease Cardiomyopathy","volume":"9","author":"Chevillard","year":"2018","journal-title":"Front Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cytogfr.2021.10.001","article-title":"Chagas Disease: Immunology of the Disease at a Glance","volume":"62","author":"Cristov\u00e3o-Silva","year":"2021","journal-title":"Cytokine Growth Factor Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.1.416","article-title":"Activation of Toll-Like Receptor-2 by Glycosylphosphatidylinositol Anchors From a Protozoan Parasite","volume":"167","author":"Campos","year":"2001","journal-title":"J Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.9.5688","article-title":"Expression of Functional TLR4 Confers Proinflammatory Responsiveness to Trypanosama Cruzi Glycoinositolphospholipids and Higher Resistance to Infection With T-Cruzi","volume":"173","author":"Oliveira","year":"2004","journal-title":"J Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.6.3515","article-title":"Cutting Edge: TLR9 and TLR2 Signaling Together Account for MyD88-Dependent Control of Parasitemia in Trypanosoma Cruzi Infection","volume":"177","author":"Bafica","year":"2006","journal-title":"J Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.3.1711","article-title":"Impaired Production of Proinflammatory Cytokines and Host Resistance to Acute Infection With Trypanosoma Cruzi in Mice Lacking Functional Myeloid Differentiation Factor 88","volume":"172","author":"Campos","year":"2004","journal-title":"J Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.ppat.1000870","article-title":"Impaired Innate Immunity in Tlr4(-\/-) Mice But Preserved CD8(+) T Cell Responses Against Trypanosoma Cruzi in Tlr4-, Tlr2-, Tlr9- or Myd88-Deficient Mice","volume":"6","author":"Oliveira","year":"2010","journal-title":"PloS Pathog"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902254","article-title":"Cutting Edge: Nucleotide-Binding Oligomerization Domain 1-Dependent Responses Account for Murine Resistance Against Trypanosoma Cruzi Infection","volume":"184","author":"Silva","year":"2010","journal-title":"J Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pntd.0002469","article-title":"NLRP3 Controls Trypanosoma Cruzi Infection Through a Caspase-1-Dependent IL-1r-Independent NO Production","volume":"7","author":"Goncalves","year":"2013","journal-title":"PloS Neglect Trop Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2020.165707","article-title":"Signaling Pathways That Regulate Trypanosoma Cruzi Infection and Immune Response","volume":"18","author":"Cerban","year":"2020","journal-title":"Biochim Et Biophys Acta-Mol Basis Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/s0020-7519(01)00322-8","article-title":"Interleukin-6 Is Required for Parasite Specific Response and Host Resistance to Trypanosoma Cruzi","volume":"32","author":"Gao","year":"2002","journal-title":"Int J Parasitol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.6.1961-1967.1996","article-title":"Interleukin-12 Mediates Resistance to Trypanosoma Cruzi in Mice and Is Produced by Murine Macrophages in Response to Live Trypomastigotes","volume":"64","author":"Aliberti","year":"1996","journal-title":"Infect Immun"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/s1286-4579(03)00176-x","article-title":"Interleukin-12 But Not Interleukin-18 Is Required for Immunity to Trypanosoma Cruzi in Mice","volume":"5","author":"Graefe","year":"2003","journal-title":"Microbes Infect"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1006\/expr.1996.0109","article-title":"Trypanosoma Cruzi: IL-10, TNF, IFN-Gamma, and IL-12 Regulate Innate and Acquired Immunity to Infection","volume":"84","author":"Abrahamsohn","year":"1996","journal-title":"Exp Parasitol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.10.7059","article-title":"TLR-Dependent Induction of IFN-Beta Mediates Host Defense Against Trypanosoma Cruzi","volume":"177","author":"Koga","year":"2006","journal-title":"J Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.5.3193","article-title":"Type I IFNs Stimulate Nitric Oxide Production and Resistance to Trypanosoma Cruzi Infection","volume":"177","author":"Costa","year":"2006","journal-title":"J Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.7.4596","article-title":"Antigen-Specific Th1 But Not Th2 Cells Provide Protection From Lethal Trypanosoma Cruzi Infection in Mice","volume":"166","author":"Kumar","year":"2001","journal-title":"J Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1128\/iai.68.1.197-204.2000","article-title":"Involvement of CD4(+) Th1 Cells in Systemic Immunity Protective Against Primary and Secondary Challenges With Trypanosoma Cruzi","volume":"68","author":"Hoft","year":"2000","journal-title":"Infect Immun"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pntd.0000733","article-title":"Specific Humoral Immunity Versus Polyclonal B Cell Activation in Trypanosoma Cruzi Infection of Susceptible and Resistant Mice","volume":"4","author":"Bryan","year":"2010","journal-title":"PloS Neglect Trop Dis"},{"key":"B21","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.144.2.717","article-title":"Depletion of CD8+ T-Cells Increases Susceptibility and Reverses Vaccine-Induced Immunity in Mice Infected with Trypanosoma-Cruzi","volume":"144","author":"Tarleton","year":"1990","journal-title":"J\u00a0Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/356338a0","article-title":"Susceptibility of Beta-2-Microglobulin-Deficient Mice to Trypanosoma-Cruzi Infection","volume":"356","author":"Tarleton","year":"1992","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1016\/j.pt.2019.08.006","article-title":"Understanding CD8(+) T Cell Immunity to Trypanosoma Cruzi and How to Improve It","volume":"35","author":"Rodriguez","year":"2019","journal-title":"Trends Parasitol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1006\/expr.2000.4498","article-title":"Trypanosoma Cruzi: Roles for Perforin-Dependent and Perforin-Independent Immune Mechanisms in Acute Resistance","volume":"94","author":"Nickell","year":"2000","journal-title":"Exp Parasitol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.ppat.1002645","article-title":"CD8(+) T-Cells Expressing Interferon Gamma or Perforin Play Antagonistic Roles in Heart Injury in Experimental Trypanosoma Cruzi-Elicited Cardiomyopathy","volume":"8","author":"Silverio","year":"2012","journal-title":"PloS Pathog"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9440(10)63019-2","article-title":"Pivotal Role of Interleukin-12 and Interferon-Gamma Axis in Controlling Tissue Parasitism and Inflammation in the Heart and Central Nervous System During Trypanosoma Cruzi Infection","volume":"159","author":"Michailowsky","year":"2001","journal-title":"Am J Pathol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1086\/381682","article-title":"Frequency of Interferon- Gamma -Producing T Cells Specific for Trypanosoma Cruzi Inversely Correlates With Disease Severity in Chronic Human Chagas Disease","volume":"189","author":"Laucella","year":"2004","journal-title":"J Infect Dis"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh387","article-title":"Trypanosoma Cruzi Modulates the Profile of Memory CD8(+) T Cells in Chronic Chagas\u2019 Disease Patients","volume":"18","author":"Albareda","year":"2006","journal-title":"Int Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/nature06013","article-title":"DAI (DLM-1\/ZBP1) Is a Cytosolic DNA Sensor and an Activator of Innate Immune Response","volume":"448","author":"Takaoka","year":"2007","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1876","article-title":"The Cytosolic Nucleic Acid Sensor LRRFIP1 Mediates the Production of Type I Interferon via a Beta-Catenin-Dependent Pathway","volume":"11","author":"Yang","year":"2010","journal-title":"Nat Immunol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1038\/ni.2091","article-title":"The Helicase DDX41 Senses Intracellular DNA Mediated by the Adaptor STING in Dendritic Cells","volume":"12","author":"Zhang","year":"2011","journal-title":"Nat Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1038\/ni.1932","article-title":"IFI16 Is an Innate Immune Sensor for Intracellular DNA","volume":"11","author":"Unterholzner","year":"2010","journal-title":"Nat Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232458","article-title":"Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway","volume":"339","author":"Sun","year":"2013","journal-title":"Science"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911267106","article-title":"Atg9a Controls dsDNA-Driven Dynamic Translocation of STING and the Innate Immune Response","volume":"106","author":"Saitoh","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0998-5","article-title":"Cryo-EM Structures of STING Reveal Its Mechanism of Activation by Cyclic GMP-AMP","volume":"567","author":"Shang","year":"2019","journal-title":"Nature"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/scisignal.2002521","article-title":"STING Specifies IRF3 Phosphorylation by TBK1 in the Cytosolic DNA Signaling Pathway","volume":"5","author":"Tanaka","year":"2012","journal-title":"Sci Signal"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700699","article-title":"NEMO-IKK Beta Are Essential for IRF3 and NF-Kappa B Activation in the cGAS-STING Pathway","volume":"199","author":"Fang","year":"2017","journal-title":"J Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00037-14","article-title":"Cytosolic-DNA-Mediated, STING-Dependent Proinflammatory Gene Induction Necessitates Canonical NF-Kappa B Activation Through TBK1","volume":"88","author":"Abe","year":"2014","journal-title":"J Virol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-019-0333-0","article-title":"STING Signaling and Host Defense Against Microbial Infection","volume":"51","author":"Ahn","year":"2019","journal-title":"Exp Mol Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2020.07.001","article-title":"STING or Sting: cGAS-STING-Mediated Immune Response to Protozoan Parasites","volume":"36","author":"Sun","year":"2020","journal-title":"Trends Parasitol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s12943-019-1087-y","article-title":"STING: A Master Regulator in the Cancer-Immunity Cycle","volume":"18","author":"Zhu","year":"2019","journal-title":"Mol Cancer"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/s41541-017-0010-z","article-title":"Engineered Trivalent Immunogen Adjuvanted With a STING Agonist Confers Protection Against Trypanosoma Cruzi Infection","volume":"2","author":"Alberti","year":"2017","journal-title":"NPJ Vaccines"},{"key":"B43","doi-asserted-by":"publisher","first-page":"e0005300","DOI":"10.1371\/journal.pntd.0005300","article-title":"Immunization With Tc52 or iIs Amino Terminal Domain Adjuvanted With C-Di-AMP Induces Th17+Th1 Specific Immune Responses and Confers Protection Against Trypanosoma Cruzi","volume":"11","author":"Matos","year":"2017","journal-title":"PloS Negl Trop Dis"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.ppat.1008474","article-title":"PARP1-cGAS-NF-Kappa B Pathway of Proinflammatory Macrophage Activation by Extracellular Vesicles Released During Trypanosoma Cruzi Infection and Chagas Disease","volume":"16","author":"Choudhuri","year":"2020","journal-title":"PloS Pathog"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.11.7917","article-title":"A Novel IFN Regulatory Factor 3-Dependent Pathway Activated by Trypanosomes Triggers IFN-Beta in Macrophages and Fibroblasts","volume":"181","author":"Chessler","year":"2008","journal-title":"J Immunol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/nature08476","article-title":"STING Regulates Intracellular DNA-Mediated, Type I Interferon-Dependent Innate Immunity","volume":"461","author":"Ishikawa","year":"2009","journal-title":"Nature"},{"key":"B47","article-title":"Therapeutic Activity and Criterion of Cure on Mice Experimentally Infected With Trypanosoma Cruzi","volume":"4","author":"Brener","year":"1962","journal-title":"Rev Inst Med Trop Sao Paulo"},{"key":"B48","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.actatropica.2007.05.019","article-title":"Development of a Real-Time PCR Assay for Trypanosoma Cruzi Detection in Blood Samples","volume":"103","author":"Piron","year":"2007","journal-title":"Acta Trop"},{"key":"B49","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.immuni.2011.05.016","article-title":"Innate Immune Recognition of an AT-Rich Stem-Loop DNA Motif in the Plasmodium Falciparum Genome","volume":"35","author":"Sharma","year":"2011","journal-title":"Immunity"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701048","article-title":"Cyclic GMP-AMP Synthase Is the Cytosolic Sensor of Plasmodium Falciparum Genomic DNA and Activates Type I IFN in Malaria","volume":"200","author":"Gallego-Marin","year":"2018","journal-title":"J Immunol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-45800-0","article-title":"Nucleic Acid Sensing Activates the Innate Cytosolic Surveillance Pathway and Promotes Parasite Survival in Visceral Leishmaniasis","volume":"9","author":"Das","year":"2019","journal-title":"Sci Rep"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.10.001","article-title":"Cross-Regulation of Two Type I Interferon Signaling Pathways in Plasmacytoid Dendritic Cells Controls Anti-Malaria Immunity and Host Mortality","volume":"45","author":"Yu","year":"2016","journal-title":"Immunity"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201488029","article-title":"Listeria Monocytogenes Induces IFN Beta Expression Through an IFI16-, cGAS- and STING-Dependent Pathway","volume":"33","author":"Hansen","year":"2014","journal-title":"EMBO J"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01929","article-title":"The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease","volume":"9","author":"Acevedo","year":"2018","journal-title":"Front Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2008.00760.x","article-title":"Rab5 Activation by Toll-Like Receptor 2 Is Required for Trypanosoma Cruzi Internalization and Replication in Macrophages","volume":"9","author":"Maganto-Garcia","year":"2008","journal-title":"Traffic"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0800621","article-title":"Trypanosoma Cruzi Triggers an Early Type I IFN Response In Vivo at the Site of Intradermal Infection","volume":"182","author":"Chessler","year":"2009","journal-title":"J Immunol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1128\/iai.74.1.125-134.2006","article-title":"The Chemokines CXCL9 and CXCL10 Promote a Protective Immune Response But Do Not Contribute to Cardiac Inflammation Following Infection With Trypanosoma Cruzi","volume":"74","author":"Hardison","year":"2006","journal-title":"Infect Immun"},{"key":"B58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pntd.0007597","article-title":"CXCR3 Chemokine Receptor Guides Trypanosoma Cruzi-Specific T-Cells Triggered by DNA\/adenovirus ASP2 Vaccine to Heart Tissue After Challenge","volume":"13","author":"Ferreira","year":"2019","journal-title":"PloS Neglect Trop Dis"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/s1471-4922(02)02283-3","article-title":"Chemokines, Inflammation and Trypanosoma Cruzi Infection","volume":"18","author":"Teixeira","year":"2002","journal-title":"Trends Parasitol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pntd.0001867","article-title":"Myocardial Chemokine Expression and Intensity of Myocarditis in Chagas Cardiomyopathy Are Controlled by Polymorphisms in CXCL9 and CXCL10","volume":"6","author":"Nogueira","year":"2012","journal-title":"PloS Neglect Trop Dis"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0065820","article-title":"Analysis of the Dynamics of Infiltrating CD4(+) T Cell Subsets in the Heart During Experimental Trypanosoma Cruzi Infection","volume":"8","author":"Sanoja","year":"2013","journal-title":"PloS One"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900852","article-title":"Chronic Human Infection With Trypanosoma Cruzi Drives CD4(+) T Cells to Immune Senescence","volume":"183","author":"Albareda","year":"2009","journal-title":"J Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.2.1098","article-title":"CXCL9 and CXCL10 Expression Are Critical for Control of Genital Herpes Simplex Virus Type 2 Infection Through Mobilization of HSV-Specific CTL and NK Cells to the Nervous System","volume":"180","author":"Thapa","year":"2008","journal-title":"J Immunol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1128\/iai.72.12.6817-6825.2004","article-title":"NK Cells Contribute to the Control of Trypanosoma Cruzi Infection by Killing Free Parasites by Perforin-Independent Mechanisms","volume":"72","author":"Lieke","year":"2004","journal-title":"Infect Immun"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.1.128-134.1996","article-title":"Regulation of Trypanosoma Cruzi Infection in Mice by Gamma Interferon and Interleukin 10: Role of NK Cells","volume":"64","author":"Cardillo","year":"1996","journal-title":"Infect Immun"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/s1286-4579(01)01461-7","article-title":"Prevalence of CD8(+)alpha Beta T Cells in Trypanosoma Cruzi-Elicited Myocarditis Is Associated With Acquisition of CD62L(Low)LFA-1(High)VLA-4(High) Activation Phenotype and Expression of IFN-Gamma-Inducible Adhesion and Chemoattractant Molecules","volume":"3","author":"dos Santos","year":"2001","journal-title":"Microbes Infect"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1993.48.637","article-title":"Characterization of Inflammatory Infiltrates in Chronic Chagasic Myocardial Lesions - Presence of Tumor Necrosis Factor-Alpha+ Cells and Dominance of Granzyme A+, Cd8+ Lymphocytes","volume":"48","author":"Reis","year":"1993","journal-title":"Am J Trop Med Hygiene"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00275-10","article-title":"Generation of Trypanosoma Cruzi-Specific CD8(+) T-Cell Immunity Is Unaffected by the Absence of Type I Interferon Signaling","volume":"78","author":"Martin","year":"2010","journal-title":"Infect Immun"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.9.5935","article-title":"IL-12 Signaling Drives CD8(+) T Cell IFN-Gamma Production and Differentiation of KLRG1(+) Effector Subpopulations During Toxoplasma Gondii Infection","volume":"180","author":"Wilson","year":"2008","journal-title":"J Immunol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.12.8576","article-title":"IL-12 Produced by Dendritic Cells Augments CD8(+) T Cell Activation Through the Production of the Chemokines CCL1 and CCL17","volume":"181","author":"Henry","year":"2008","journal-title":"J Immunol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800016","article-title":"IL-6 Promotes T Cell Proliferation and Expansion Under Inflammatory Conditions in Association With Low-Level ROR Gamma T Expression","volume":"201","author":"Li","year":"2018","journal-title":"J Immunol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00626","article-title":"IL-6 Improves the Nitric Oxide-Induced Cytotoxic Cd8+T Cell Dysfunction in Human Chagas Disease","volume":"7","author":"Sanmarco","year":"2016","journal-title":"Front Immunol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050821","article-title":"Type I Interferons Act Directly on CD8 T Cells to Allow Clonal Expansion and Memory Formation in Response to Viral Infection","volume":"202","author":"Kolumam","year":"2005","journal-title":"J Exp Med"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1997.4335","article-title":"An In Situ Quantitative Immunohistochemical Study of Cytokines and IL-2R(+) in Chronic Human Chagasic Myocarditis: Correlation With the Presence of Myocardial Trypanosoma Cruzi Antigens","volume":"83","author":"Reis","year":"1997","journal-title":"Clin Immunol Immunopathol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.775346\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,22]],"date-time":"2023-01-22T22:50:44Z","timestamp":1674427844000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.775346\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,14]]},"references-count":74,"alternative-id":["10.3389\/fimmu.2021.775346"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.775346","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,14]]},"article-number":"775346"}}