Efficient capture of infected neutrophils by dendritic cells in the skin inhibits the early anti-leishmanial response (67.13)

Abstract

Abstract Neutrophils and dendritic cells (DC) converge at sites of acute inflammation in the skin following pathogen deposition by the bites of arthropod vectors or by needle injection. How neutrophils might interact with and modulate the function of DCs in these inflammatory settings has not been previously addressed. Neutrophils are the predominant recruited and infected cells during the earliest stage of Leishmania major infection in the skin. The infected neutrophils recovered from the skin expressed elevated levels of apoptotic markers and were preferentially captured by dermal DCs, the majority of which acquired their parasites via uptake of infected neutrophils. Neutrophil depletion augmented the expression of activation markers on infected DCs and their ability to present Leishmania antigen ex vivo, and markedly enhanced CD4+ T cell priming against parasite-derived antigen in vivo. The findings suggest that L. major exploits the apoptotic cell clearance function of DCs to suppress the development of acquired resistance until the acute neutrophilic response is resolved.