Protective immune response mediated by neutrophils in experimental visceral leishmaniasis is enhanced by IL-32γ

Abstract

Neutrophils are important cells in protection against microbial infections including visceral leishmaniasis (VL). It is well known that IL-32γ increases the protective T helper 17 cell mediated immune response against Leishmania infantum. Thus, in this study we evaluated whether IL-32 γ can increase the protective role of neutrophils against VL. In comparison with wild type (WT) mice, transgenic mice for human IL-32 γ (IL-32 γ Tg) presented a higher frequency and absolute number of neutrophils in both spleen and liver after the establishment of L. infantum infection. The IL-32 concentrations correlated with neutrophil numbers in the infected tissues. The IL-32 γ -induced recruitment of neutrophils was dependent on IL-17, since inhibition of Th17 T cells generation and IL-17 production with digoxin treatment reversed the effects of IL-32 γ. In murine neutrophils, the presence of IL-32 γ enhanced the phagocytosis of L. infantum via CR3. In addition, murine IL-32 γ Tg neutrophils were able to kill L. infantum due to the increased production of ROS when compared with WT neutrophils. In fact, IL-32 γ Tg mice lost their ability to control infection by L. infantum when neutrophils were depleted. In parallel, treatment of human neutrophils with recombinant IL-32 γ increased phagocytosis and ROS-dependent killing of L. infantum, similarly to murine IL-32 γ Tg neutrophils. The data show that IL-32 γ induces neutrophil recruitment to organs affected by VL and increases phagocytosis and killing of L. infantum by neutrophils. Together, data indicate the pivotal axis IL-32 γ -Th17-neutrophils to control VL.

Keywords: IL-32; Immune response; Leishmania infantum; Neutrophils; Visceral leishmaniasis.