The presence of Tregs does not preclude immunity to reinfection with Leishmania braziliensis.
Leishmania spp. cause a broad spectrum of diseases collectively known as leishmaniasis. Leishmania braziliensis is the main etiological agent of American cutaneous leishmaniasis and mucocutaneous leishmaniasis. During experimental infection with L. braziliensis, BALB/c mice develop an adaptive immune response that is associated with lesion healing and, in parallel, parasite persistence within draining lymph nodes (dLNs). In the Leishmania major model of cutaneous leishmaniasis, regulatory T cells (Tregs) play an important role in immune regulation, preventing pathological immune responses but at the same time precluding sterile cure. In this study we investigated the role of Tregs during experimental infection with L. braziliensis. CD4(+)CD25(+) T cells were detected throughout the duration of clinical disease both at the ear and in dLNs of infected mice. These cells expressed Treg markers such as glucocorticoid-induced TNF-receptor-related protein (GITR), the α chain of the αεβ7 integrin (CD103), and the forkhead/winged helix transcription factor, Foxp3, and were able to suppress the proliferation of CD4(+)CD25(-) cells. Importantly, a high frequency of Foxp3(+) cells accumulated at the site of infection and in dLNs. We next investigated the outcome of a reinfection with L. braziliensis in terms of Treg distribution and disease reactivation. Interestingly, a secondary inoculation with L. braziliensis did not preclude an efficient recall response to L. braziliensis at a distal site, despite the presence of Tregs. Within dLNs, reinfection did not promote parasite dissemination or a differential recruitment of either CD4(+)CD25(+)Foxp3(+) or CD4(+)IL-10(+) T cells. On the contrary, parasites were mainly detected in the LN draining the primary infection site where a high frequency of CD4(+)IFN-γ(+) T cells was also present. Collectively these data show that during experimental infection, Tregs are present in healed mice but this population does not compromise an effective immune response upon reinfection with L. braziliensis.
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Rua Waldemar Falcão, 121, Salvador, BA, Brazil.
Sarah
S
C Falcão
Tatiana R
TR
de Moura
Jorge
J
Clarêncio
Cláudia
C
Brodskyn
Aldina
A
Barral
Camila I
CI
de Oliveira
D000818:Animals; D005260:Female; D006801:Humans; D007109:Immunity; D007892:Leishmania braziliensis / Q000502:physiology*; D007896:Leishmaniasis / Q000276:immunology* / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*