{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:58:39Z","timestamp":1753891119570,"version":"3.41.2"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:italic>Eimeria<\/jats:italic>, a cousin of malarial parasites, causes coccidiosis that results in huge losses in the poultry industry. Although live coccidiosis vaccines have been developed and used widely for the successful control of the disease, the mechanism underlying protective immunity remains largely unknown. Using <jats:italic>Eimeria falciformis<\/jats:italic> as a model parasite, we observed that tissue-resident memory CD8<jats:sup>+<\/jats:sup> T (Trm) cells accumulated in cecal lamina propria following <jats:italic>E. falciformis<\/jats:italic> infection in mice, especially after reinfection. In convalescent mice challenged with a second infection, <jats:italic>E. falciformis<\/jats:italic> burden diminished within 48-72\u00a0h. Deep-sequencing revealed that CD8<jats:sup>+<\/jats:sup> Trm cells were characterized by rapid up-regulation of effector genes encoding pro-inflammatory cytokines and cytotoxic effector molecules. While FTY720 (Fingolimod) treatment prevented the trafficking of CD8<jats:sup>+<\/jats:sup> T cells in peripheral circulation and exacerbated primary <jats:italic>E. falciformis<\/jats:italic> infection, such treatment had no impact on the expansion of CD8<jats:sup>+<\/jats:sup> Trm cells in convalescent mice receiving secondary infection. Adoptive transfer of cecal CD8<jats:sup>+<\/jats:sup> Trm cells conferred immune protection in na\u00efve mice, indicating that these cells provide direct and effective protection against infection. Overall, our findings not only explain a protective mechanism of live oocyst-based anti-<jats:italic>Eimeria<\/jats:italic> vaccines but also provide a valuable correlate for assessing vaccines against other protozoan diseases.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1128637","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:33:03Z","timestamp":1676392383000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Tissue-resident, memory CD8+ T cells are effective in clearing intestinal Eimeria falciformis reinfection in mice"],"prefix":"10.3389","volume":"14","author":[{"given":"Fangyun","family":"Shi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sixin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinming","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianyong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xun","family":"Suo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01261","article-title":"Potential sabotage of host cell physiology by apicomplexan parasites for their survival benefits","volume":"8","author":"Chakraborty","year":"2017","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1017\/s0031182000046734","article-title":"Eimeria falciformis (Eimer, 1870) in specific pathogen free and gnotobiotic mice","volume":"71","author":"Owen","year":"1975","journal-title":"Parasitology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02732","article-title":"Involvement of T cell immunity in avian coccidiosis","volume":"10","author":"Kim","year":"2019","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.10.003","article-title":"Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens","volume":"4","author":"Zhao","year":"2008","journal-title":"Cell Host Microbe"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5489.92","article-title":"Dynamics of T lymphocyte responses: intermediates, effectors, and memory cells","volume":"290","author":"Lanzavecchia","year":"2000","journal-title":"Science"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01190-10","article-title":"Heterologous plasmid DNA prime-recombinant human adenovirus 5 boost vaccination generates a stable pool of protective long-lived CD8(+) T effector memory cells specific for a human parasite, trypanosoma cruzi","volume":"79","author":"Rigato","year":"2011","journal-title":"Infect Immun"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141548","article-title":"Effector and memory CTL differentiation","volume":"25","author":"Williams","year":"2007","journal-title":"Annu Rev Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2744","article-title":"The developmental pathway for CD103(+)CD8+ tissue-resident memory T cells of skin","volume":"14","author":"Mackay","year":"2013","journal-title":"Nat Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1126\/science.1254536","article-title":"T Cell memory. resident memory CD8 T cells trigger protective innate and adaptive immune responses","volume":"346","author":"Schenkel","year":"2014","journal-title":"Science"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.03.007","article-title":"Oral infection drives a distinct population of intestinal resident memory CD8(+) T cells with enhanced protective function","volume":"40","author":"Sheridan","year":"2014","journal-title":"Immunity"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/s0041-1345(98)01975-7","article-title":"FTY720, a novel immunosuppressant, induces sequestration of circulating lymphocytes by acceleration of lymphocyte homing","volume":"31","author":"Chiba","year":"1999","journal-title":"Transplant Proc"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2009.12.005","article-title":"CD8+ cells protect mice against reinfection with the intestinal parasite eimeria falciformis","volume":"12","author":"Pogonka","year":"2010","journal-title":"Microbes Infect"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1017\/s0031182000074515","article-title":"Immune control of murine coccidiosis: CD4+ and CD8+ T lymphocytes contribute differentially in resistance to primary and secondary infections","volume":"105","author":"Rose","year":"1992","journal-title":"Parasitology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2307\/3276644","article-title":"Effects of the immune chicken on the endogenous stages of eimeria tenella","volume":"53","author":"Leathem","year":"1967","journal-title":"J Parasitol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.2307\/3282485","article-title":"Eimeria maxima (Apicomplexa): a comparison of sporozoite transport in naive and immune chickens","volume":"74","author":"Riley","year":"1988","journal-title":"J Parasitol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.12.5283-5290.1992","article-title":"Intestinal changes associated with expression of immunity to challenge with eimeria vermiformis","volume":"60","author":"Rose","year":"1992","journal-title":"Infect Immun"},{"key":"B17","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1017\/s0031182000054470","article-title":"The effect of immunity on the early events in the life-cycle of eimeria tenella in the caecal mucosa of the chicken","volume":"88","author":"Rose","year":"1984","journal-title":"Parasitology"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-095954","article-title":"Memory T cell subsets, migration patterns, and tissue residence","volume":"31","author":"Mueller","year":"2013","journal-title":"Annu Rev Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0123-x","article-title":"Adaptive immune responses to primary and secondary dengue virus infections","volume":"19","author":"St John","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.1016\/j.jaci.2018.11.048","article-title":"Inhibitory checkpoint receptors control CD8(+) resident memory T cells to prevent skin allergy","volume":"143","author":"Gamradt","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-396548-6.00008-1","article-title":"Behavior and function of tissue-resident memory T cells","volume":"114","author":"Ariotti","year":"2012","journal-title":"Adv Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2568","article-title":"Sensing and alarm function of resident memory CD8(+) T cells","volume":"14","author":"Schenkel","year":"2013","journal-title":"Nat Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.08.019","article-title":"Transforming growth factor-beta signaling controls the formation and maintenance of gut-resident memory T cells by regulating migration and retention","volume":"39","author":"Zhang","year":"2013","journal-title":"Immunity"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010201107","article-title":"Memory T cells persisting within the brain after local infection show functional adaptations to their tissue of residence","volume":"107","author":"Wakim","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nature10851","article-title":"Skin infection generates non-migratory memory CD8+ T(RM) cells providing global skin immunity","volume":"483","author":"Jiang","year":"2012","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1172\/Jci44675","article-title":"CD8(+) T cells with an intraepithelial phenotype upregulate cytotoxic function upon influenza infection in human lung","volume":"121","author":"Piet","year":"2011","journal-title":"J Clin Invest"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1202288109","article-title":"Long-lived epithelial immunity by tissue-resident memory T (TRM) cells in the absence of persisting local antigen presentation","volume":"109","author":"Mackay","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"B28","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/nri.2015.3","article-title":"Tissue-resident memory T cells: local specialists in immune defence","volume":"16","author":"Mueller","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(73)90208-6","article-title":"Immunity to the protozoan parasite eimeria nieschulzi in inbred CD-f rats","volume":"7","author":"Liburd","year":"1973","journal-title":"Cell Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.5.1808-1813.1997","article-title":"Oral vaccination against coccidiosis: responses in strains of mice that differ in susceptibility to infection with eimeria vermiformis","volume":"65","author":"Rose","year":"1997","journal-title":"Infect Immun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.1982.tb00429.x","article-title":"Immunity to coccidia in chickens: adoptive transfer with peripheral blood lymphocytes and spleen cells","volume":"4","author":"Rose","year":"1982","journal-title":"Parasite Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1126\/science.1254803","article-title":"T Cell memory. skin-resident memory CD8(+) T cells trigger a state of tissue-wide pathogen alert","volume":"346","author":"Ariotti","year":"2014","journal-title":"Science"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa8205","article-title":"VACCINES. a mucosal vaccine against chlamydia trachomatis generates two waves of protective memory T cells","volume":"348","author":"Stary","year":"2015","journal-title":"Science"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.08.078","article-title":"Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites","volume":"20","author":"Kumar","year":"2017","journal-title":"Cell Rep"},{"key":"B35","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/s41590-017-0029-3","article-title":"Intravital mucosal imaging of CD8(+) resident memory T cells shows tissue-autonomous recall responses that amplify secondary memory","volume":"19","author":"Beura","year":"2018","journal-title":"Nat Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-017-0027-5","article-title":"Local proliferation maintains a stable pool of tissue-resident memory T cells after antiviral recall responses","volume":"19","author":"Park","year":"2018","journal-title":"Nat Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.4.2079","article-title":"Cutting edge: gut microenvironment promotes differentiation of a unique memory CD8 T cell population","volume":"176","author":"Masopust","year":"2006","journal-title":"J Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151916","article-title":"Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection","volume":"213","author":"Steinbach","year":"2016","journal-title":"J Exp Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3589","article-title":"Programs for the persistence, vigilance and control of human CD8(+) lung-resident memory T cells","volume":"17","author":"Hombrink","year":"2016","journal-title":"Nat Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad2035","article-title":"Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes","volume":"352","author":"Mackay","year":"2016","journal-title":"Science"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/cells10082143","article-title":"Single-cell transcriptomics reveals core regulatory programs that determine the heterogeneity of circulating and tissue-resident memory CD8(+) T cells","volume":"10","author":"Chen","year":"2021","journal-title":"Cells"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aaz6894","article-title":"Early precursors and molecular determinants of tissue-resident memory CD8(+) T lymphocytes revealed by single-cell RNA sequencing","volume":"5","author":"Kurd","year":"2020","journal-title":"Sci Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1128637\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:33:07Z","timestamp":1676392387000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1128637\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,14]]},"references-count":42,"alternative-id":["10.3389\/fimmu.2023.1128637"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1128637","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2023,2,14]]},"article-number":"1128637"}}