Interleukin 17A acts synergistically with interferon γ to promote protection against Leishmania infantum infection.

Interleukin 17 (IL-17) is an inflammatory cytokine that plays a protective role against intracellular parasites. The role of IL-17 during Leishmania infection remains controversial and poorly defined. We evaluated whether IL-17 participates in the host immune response to Leishmania infantum. IL-17A is present in sera from patients with visceral leishmaniasis and decreases after successful treatment. In C57BL/6 infected mice, higher production of IL-17A coincided with the peak of parasitism. Il17ra(-/-) mice were more susceptible to infection and also exhibited reduced inflammatory infiltration and interferon γ (IFN-γ)-expressing CD4+ T-cell frequencies than wild-type mice. The frequencies of FoxP3+ CD4+ T cells and interleukin 10 (IL-10)-expressing CD4+ T cells were increased in Il17ra(-/-) mice. We also demonstrated that IL-17A acts synergistically with IFN-γ to potentiate NO production and leishmanicidal activity in infected macrophages. Therefore, our results indicate that L. infantum induces IL-17A production, which promotes the control of parasite replication by strengthening T-helper type 1 responses and NO production and prevents regulatory T-cell and IL-10-expressing T-cell expansion.

Adaptive immunity to retroelements promotes barrier integrity.

Maintenance of tissue integrity is a requirement of host survival. This mandate is of prime importance at barrier sites that are constitutively exposed to the environment. Here, we show that exposure of the skin to non-inflammatory xenobiotics promotes tissue repair; more specifically, mild detergent exposure promotes the reactivation of defined retroelements leading to the induction of retroelement-specific CD8+ T cells. These T cell responses are Langerhans cell dependent and establish tissue residency within the skin. Upon injury, retroelement-specific CD8+ T cells significantly accelerate wound repair via IL-17A. Collectively, this work demonstrates that tonic environmental exposures and associated adaptive responses to retroelements can be coopted to preemptively set the tissue for maximal resilience to injury.

T1/ST2 deficient mice display protection against Leishmania infantum experimental infection.

T1/ST2 is a surface marker selectively expressed on type 2 helper (TH2) effector cells. As Leishmania infection in susceptible BALB/c mice have ascribed to a polarized TH2 response, this study aim to investigate the T1/ST2 (the receptor for IL-33), as a typical TH2 marker in the postulation that a shift towards a beneficial TH1 response would occur in the absence of ST2. For this, ST2 knockout (ST2-/-) and WT BALB/c mice were experimentally infected in the retro-orbital sinus with L. infantum. We showed that ST2-/- animals displayed better control of parasite burden in both spleen and liver tissues at different time points of chronic phases, and reduced spleenomegaly and hepatomegaly compared with the wild-type (WT) mice. This was associated with increased in the IFN-γ levels and expression by CD4+ and CD8+ lymphocytes. The inflammatory response encompasses transaminases (AST and ALT) releases and NO productions were remarkably lower in ST2-/- mice compared with WT. These data suggest that, ST2-/-) exert protection against L. infantum infection and probably shift the immune response toward TH1 induction.