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Paradoxically, repeated low-dose intradermal infections predispose mice to enhanced susceptibility to an otherwise noninfectious dose challenge. Here, we explored the mechanisms responsible for this low-dose-induced susceptibility to subsequent low-dose challenge infection. We found that akin to intraperitoneal infection, low-dose intradermal infection led to production of interleukin-10 (IL-10), IL-6, IL-12, tumor necrosis factor alpha (TNF-\u03b1), transforming growth factor \u03b2 (TGF-\u03b2), and gamma interferon (IFN-\u03b3) by spleen and draining lymph node cells. Interestingly, despite the absence of parasitemia, low-dose intradermal infection led to expansion of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup>cells (T regulatory cells [Tregs]) in both the spleens and lymph nodes draining the infection site. Depletion of Tregs by anti-CD25 monoclonal antibody (MAb) treatment during primary infection or before challenge infection following repeated low-dose infection completely abolished the low-dose-induced enhanced susceptibility. In addition, Treg depletion was associated with dramatic reduction in serum levels of TGF-\u03b2 and IL-10. Collectively, these findings show that low-dose intradermal infection leads to rapid expansion of Tregs, and these cells mediate enhanced susceptibility to subsequent infection.<\/jats:p>","DOI":"10.1128\/iai.01028-13","type":"journal-article","created":{"date-parts":[[2013,12,17]],"date-time":"2013-12-17T03:16:28Z","timestamp":1387250188000},"page":"1074-1083","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["Low-Dose Intradermal Infection with Trypanosoma congolense Leads to Expansion of Regulatory T Cells and Enhanced Susceptibility to Reinfection"],"prefix":"10.1128","volume":"82","author":[{"given":"Chukwunonso","family":"Onyilagha","sequence":"first","affiliation":[{"name":"Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ifeoma","family":"Okwor","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiby","family":"Kuriakose","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rani","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jude","family":"Uzonna","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada"},{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-072X-9-57"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33945"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.11.44"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4922(00)01851-1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0308-521X(98)00086-9"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/381151"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-003-0844-3"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.3.1724"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3024.1998.00156.x"},{"key":"e_1_3_3_11_2","first-page":"119","article-title":"Macrophages as mediators of immunosuppression in murine African trypanosomiasis","volume":"117","author":"Askonas BA","year":"1985","unstructured":"AskonasBA. 1985. 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