The prominent role of neutrophils during the initial phase of infection by Leishmania parasites

Abstract

Neutrophils are rapidly and massively recruited to the site of Leishmania inoculation, where they phagocytose the parasites, some of which are able to survive within these first host cells. Neutrophils can thus provide a transient safe shelter for the parasites, prior to their entry into macrophages where they will replicate. In addition, neutrophils release and synthesize rapidly several factors including cytokines and chemokines. The mechanism involved in their rapid recruitment to the site of parasite inoculation, as well as the putative consequences of their massive presence on the microenvironment of the focus of infection will be discussed in the context of the development of the Leishmania-specific immune response.

Figure 1

Exposure of neutrophils to L. major decreases spontaneous but not macrophage-induced apoptosis. L. major-recruited C57BL/6 neutrophils (PMNs) and macrophages (Mϕ) were isolated from the peritoneal cavity 4 hours or 24 hours after L. major injection i.p., respectively. (a) MACS-purified PMNs were cultured for 24 hours in presence or in absence of metacyclic L. major (L. major : PMN ratio 1 : 5). Cells were collected, labeled with Annexin-V, 7AAD, and the 1A8 mAb (Ly6G) and PMN apoptosis analyzed by FACS, gating on the 1A8⁺ PMN population. Early apoptotic cells are Annexin-V⁺ 7AAD⁻, and late apoptotic/necrotic cells are Annexin-V⁺7AAD⁺. (b) PMNs were cultured in presence of fixed Mϕ(PMN : Mϕ1 : 2) with or without parasites, and 24 hours later, neutrophils were analyzed as in A. Data are representative of three independent experiments.

Figure 2

Early neutrophil recruitment to the site of L. major infection and its potential influence on the development L. major specific-immune response. (1) L. major parasites are transmitted by the bite of the sand fly. (2) This induces rapid and massive recruitment of neutrophils to the site of parasite inoculation, a process not defined, that may involve different host and/or parasite-derived factors such as IL-8, KC(Gro-α), MIP-2 (Gro-β), IL-17, TNF, and LCF. (3) L. major parasites induce chemokine and cytokine secretion by neutrophils that attract and/or activate inflammatory cells at the site of infection. Crosstalk between neutrophils and the different cell types present or recruited to the site of infection, as well as interaction between these cells, will contribute to determine the type and magnitude of the L. major specific immune response that will develop.