Apoptotic cell clearance of Leishmania major-infected neutrophils by dendritic cells inhibits CD8⁺ T-cell priming in vitro by Mer tyrosine kinase-dependent signaling.

Neutrophils are the predominant recruited and infected cells during the early stages of Leishmania major infection in the skin, and depletion of neutrophils promotes immunity to infection transmitted by sand fly bite. In order to better understand how the acute neutrophilic response suppresses immunity, we assessed the consequences of the interaction between neutrophils recovered from the skin-inoculation site and bone marrow-derived dendritic cells (DCs) in vitro. The capture of infected, apoptotic neutrophils by the DCs completely inhibited their cross-presentation function that was dependent on engagement of the receptor tyrosine kinase Mer on the DCs. The capture of uninfected neutrophils, or neutrophils infected with Toxoplasma gondii, had only slight immunomodulatory effects. These studies define the clearance of infected, apoptotic neutrophils by DCs and Mer receptor signaling as central to the early immune evasion strategies of L. major, with relevance to other vector-borne pathogens delivered by bite to the skin.

Neutrophils, apoptosis and phagocytic clearance: an innate sequence of cellular responses regulating intramacrophagic parasite infections.

In complex organisms, apoptosis is a constitutive cell death process that is involved in physiological regulation of cell numbers and that can also be induced in the course of inflammatory and immune responses. Neutrophils are among the first cells recruited during inflammation. Neutrophils constitutively die by apoptosis at inflamed sites, and are ingested by macrophages. Recent studies investigated how phagocytic clearance of senescent neutrophils influences the survival of intracellular protozoan parasites that have been phagocytosed by, or have invaded phagocytes. The results indicate that neutrophil clearance plays an unexpected role in regulation of intramacrophagic protozoan parasite infection.