Exposure to <i>Leishmania braziliensis</i> Triggers Neutrophil Activation and Apoptosis

<div><p>Background</p><p>Neutrophils are the first line of defense against invading pathogens and are rapidly recruited to the sites of <i>Leishmania</i> inoculation. During <i>Leishmania braziliensis</i> infection, depletion of inflammatory cells significantly increases the parasite load whereas co-inoculation of neutrophils plus <i>L</i>. <i>braziliensis</i> had an opposite effect. Moreover, the co-culture of infected macrophages and neutrophils also induced parasite killing leading us to ask how neutrophils alone respond to an <i>L</i>. <i>braziliensis</i> exposure. Herein we focused on understanding the interaction between neutrophils and <i>L</i>. <i>braziliensis</i>, exploring cell activation and apoptotic fate.</p><p>Methods and Findings</p><p>Inoculation of serum-opsonized <i>L</i>. <i>braziliensis</i> promastigotes in mice induced neutrophil accumulation <i>in vivo</i>, peaking at 24 h. <i>In vitro</i>, exposure of thyoglycollate-elicited inflammatory or bone marrow neutrophils to <i>L</i>. <i>braziliensis</i> modulated the expression of surface molecules such as CD18 and CD62L, and induced the oxidative burst. Using mCherry-expressing <i>L</i>. <i>braziliensis</i>, we determined that such effects were mainly observed in infected and not in bystander cells. Neutrophil activation following contact with <i>L</i>. <i>braziliensis</i> was also confirmed by the release of TNF-α and neutrophil elastase. Lastly, neutrophils infected with <i>L</i>. <i>braziliensis</i> but not with <i>L</i>. <i>major</i> displayed markers of early apoptosis.</p><p>Conclusions</p><p>We show that <i>L</i>. <i>braziliensis</i> induces neutrophil recruitment <i>in vivo</i> and that neutrophils exposed to the parasite <i>in vitro</i> respond through activation and release of inflammatory mediators. This outcome may impact on parasite elimination, particularly at the early stages of infection.</p>