Semaphorin 3E Promotes Susceptibility to <i>Leishmania major</i> Infection in Mice by Suppressing CD4+ Th1 Cell Response

Abstract Protective immunity to cutaneous leishmaniasis is mediated by IFN-γ–secreting CD4+ Th1 cells. IFN-γ binds its receptor on Leishmania-infected macrophages, resulting in their activation, production of NO, and subsequent destruction parasites. This study investigated the role Semaphorin 3E (Sema3E) host Leishmania major infection mice. We observed a significant increase Sema3E expression at site different timepoints following L. infection. Sema3E-deficient (Sema3E knockout [KO]) mice were highly resistant infection, as evidenced significantly (p &amp;lt; 0.05–0.01) reduced lesion sizes lower parasite burdens times postinfection when compared with infected wild-type counterpart The enhanced resistance KO was associated 0.05) increased T CD11c+ cells from displayed costimulatory molecules IL-12p40 more efficient inducing differentiation Leishmania-specific than Furthermore, purified showed propensity differentiate into vitro, this inhibited addition recombinant vitro. These findings collectively show that negative regulator protective suggest neutralization may be potential therapeutic option for treating individuals suffering leishmaniasis.