FcRγIIA  attenuates cutaneous leishmaniasis by modulating Lyn, Fyn and SHP-1 activity

Abstract Background Leishmania is responsible for a neglected tropical disease affecting millions of people around the world and could potentially spread more due to climate change. Despite the complexity and effectiveness of the immune response, the parasite has developed many strategies to evade it and to take control of the host cell in favor of its replication. These evasion strategies start at earlier stages of the infection by hijacking immune receptors to silence the cellular response. Methods For in vivo studies, CD32a transgenic mice and the corresponding WT were infected with Leishmania major Friedlin strain. For in cellulo studies, BMDMs isolated from WT or CD32a transgenic mice, as well as differentiated control or CD32a knock down THP-1 were infected with 2 species of Leishmania, Leishmania major and Leishmania Tropica. Results We have investigated how Leishmania may use the Fc receptor FcγRIIA/CD32a and the signaling pathways downstream to evade the host immune response. In vivo, expression of FcγRIIA/CD32a accelerates the signs of inflammation but prevents the formation of necrotic lesions after Leishmania infection. In infected macrophages, the presence of FcγRIIA/CD32a does not affect the secretion of pro-inflammatory cytokines while the balance between ITAMa and ITAMi proteins is disturbed with an improved Fyn and Lyn activation. Unexpectedly, infection with Leishmania tropica but not Leishmania major triggered an intracytoplasmic processing of FcγRIIA/CD32a. Conclusions Our observations underscore the significance of FcγRIIA/CD32a in cutaneous leishmaniasis and its possible use as a therapeutic target.