EBI3 impacts Leishmania braziliensis-induced inflammation in localized cutaneous leishmaniasis

Abstract Localized Cutaneous Leishmaniasis (LCL) can ultimately progresses to chronic ulcerated lesion with strong local inflammatory reaction. We hypothesized that regulatory cytokines, such as Interleukin-27 (IL-27) and interleukin-35 (IL-35) can play a role in susceptibility to Leishmania braziliensis infection. IL-27 and IL-35 are members of the interleukin-12 (IL-12) family structurally related by sharing Epstein–Barr virus-induced gene 3 (EBI3), which forms a heterodimer either with the p28 subunit to build IL-27 or with IL-12p35 to form IL-35. We used RT-PCR and Immunohistochemistry analysis to detect high expression of IL-27 and IL-35 subunits in the patients biopsies compared to healthy controls, suggesting that these cytokines can be involved in immunopathology induced by the infection. Moreover, L. braziliensis infection also induced IL-27/35 mRNA expression both in vitro and in vivo. We here analysed the function of EBI3 during infection with the intracellular parasite Leishmania braziliensis. We showed that EBI3 defficient mice displayed bigger lesion and an elevated inflammatory immune response in the ear compared to Wild-type mice with similar parasites levels in the ear and lymph nodes. The lack of EBI3 led to an increased expression of T helper type 1(Th1-), Th2- and Th17-derived cytokines in the infected ears. So far, our results demonstrate that EBI3 acts as a regulator of inflammatory immune responses in experimental cutaneous leishmaniasis, although, it is not required for control of L. braziliensis infection. Financial Support: CAPES, FAPESP, CRID.