Abstract
Neutrophils represent one of the first immune cell types recruited to sites of infection, where they can control pathogens by phagocytosis and cytotoxic mechanisms. Intracellular pathogens such as Leishmania major can hijack neutrophils to establish an efficient infection. However the dynamic interactions of neutrophils with the pathogen and other cells at the site of the infection are incompletely understood. Here, we have investigated the role of Ly6G, a homolog of the human CD177 protein, which has been shown to interact with cell adhesion molecules, and serves as a bona fide marker for neutrophils in mice. We show that Ly6G deficiency decreases the initial infection rate of neutrophils recruited to the site of infection. Although the uptake of L. major by subsequently recruited monocytes was tightly linked with the concomitant uptake of neutrophil material, this process was not altered by Ly6G deficiency of the neutrophils. Instead, we observed by intravital 2-photon microscopy that Ly6G-deficient neutrophils entered the site of infection with delayed initial recruitment kinetics. Thus, we conclude that by promoting neutrophils’ ability to efficiently enter the site of infection, Ly6G contributes to the early engagement of intracellular pathogens by the immune system.
Highlights
Neutrophils represent one of the first immune cell types recruited to sites of infection, where they can control pathogens by phagocytosis and cytotoxic mechanisms
As neutrophils have been shown to influence the recruitment of monocyte-derived macrophage- and dendritic cell-like phagocytes, we determined the fractions of these cells in the infected ear (Fig. 1c)
Ly6G is among the most important markers used to identify neutrophils in m ice[48,62], whether it has a function in enabling neutrophils to be recruited to and engage pathogens during infection is unclear
Summary
Neutrophils represent one of the first immune cell types recruited to sites of infection, where they can control pathogens by phagocytosis and cytotoxic mechanisms. (f) Unchanged parasite burden in L. major infected ear determined by limiting dilution 7 and 28 days p.i. Horizontal bars represent mean; ns not significant as determined by two-way ANOVA (time, genotype) with Bonferroni post test for the genotype. (g) Histograms depicting the infection rate of infected neutrophils (left panel), mo-macro (middle panel) and mo-DCs (right panel) after infection with EGFP-expressing L. major 2, 7 and 28 days p.i. in L y6Gcre/+ and Ly6Gcre/cre mice. Proportion of infected neutrophils (h), mo-macro (i) and mo-DCs (j) analyzed via EGFP fluorescence of the parasite within the cells at day 2, 7 and 28 p.i. in L y6Gcre/+ and Ly6Gcre/cre mice.
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