The influence of early neutrophil-Leishmania interactions on the host immune response to infection

Abstract

Neutrophils are the first cells recruited to the dermal site of Leishmania infection following injection by needle or sand fly bite. The role of neutrophils in either promoting or suppressing host immunity remains controversial. We discuss the events driving neutrophil recruitment, their interaction with the parasite and apoptotic fate, and the nature of their encounters with other innate cells. We suggest that the influence of the neutrophil response on infection outcome critically depends on the timing of their recruitment and the tissue environment in which it occurs.

Keywords: Leishmania; apoptosis; dendritic cells; immune response; inflammation; macrophages; neutrophils; sand fly.

Figure 1

The immunomodulatory role of neutrophils at the site of Leishmania transmission by sand fly bite. Metacyclic promastigotes deposited in the skin by infected sand flies are taken up primarily by neutrophils that are rapidly recruited to the site of bite. Infected neutrophils recovered from the ear dermis have accelerated expression of apoptotic markers, with the majority dying in situ to release viable parasites that may be better adapted for intracellular survival and growth following their uptake by macrophages. The engulfment of infected and uninfected cells or apoptotic bodies by macrophages may inhibit the activation of infected macrophages in the inflammatory site. The initial infection of dermal DCs appears to take place primarily in the context of their capture of parasitized neutrophils. This encounter strongly reduces their priming capacity and consequently delays the immune response against the parasite until the acute neutrophilic response is resolved.