title: Low-dose intradermal infection with trypanosoma congolense leads to expansion of regulatory T cells and enhanced susceptibility to reinfection.
abstract: BALB/c mice are highly susceptible to experimental intraperitoneal Trypanosoma congolense infection. However, a recent report showed that these mice are relatively resistant to primary intradermal low-dose infection. 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-α), transforming growth factor β (TGF-β), and gamma interferon (IFN-γ) by spleen and draining lymph node cells. Interestingly, despite the absence of parasitemia, low-dose intradermal infection led to expansion of CD4+ CD25+ Foxp3+ 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-β 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.
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Chukwunonso
authors.initials: C
authors.lastname: Onyilagha
authors.forename: Ifeoma
authors.initials: I
authors.lastname: Okwor
authors.forename: Shiby
authors.initials: S
authors.lastname: Kuriakose
authors.forename: Rani
authors.initials: R
authors.lastname: Singh
authors.forename: Jude
authors.initials: J
authors.lastname: Uzonna
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D004198:Disease Susceptibility / Q000276:immunology* / Q000469:parasitology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology; D013154:Spleen / Q000276:immunology / Q000469:parasitology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000469:parasitology; D016212:Transforming Growth Factor beta / Q000276:immunology; D014348:Trypanosoma congolense / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000276:immunology* / Q000469:parasitology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D007378:Interleukins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma