Neutrophils have a protective role during early stages of Leishmania amazonensis infection in BALB/c mice

Parasite Immunol. 2014 Jan;36(1):13-31. doi: 10.1111/pim.12078.

Abstract

Neutrophils are involved in the early stages of immune responses to pathogens. Here, we investigated the role of neutrophils during the establishment of Leishmania amazonensis infection in BALB/c and C57BL/6 mice. First, we showed an accumulation of neutrophils between 6 and 24 h post-infection, followed by a reduction in neutrophil numbers after 72 h. Next, we depleted neutrophils prior to infection using RB6-8C5 or 1A8 mAb. Neutrophil depletion led to faster lesion development, increased parasite numbers and higher arginase activity during the first week of infection in BALB/c mice, but not in C57BL/6 mice. Increased susceptibility was accompanied by augmented levels of anti-L. amazonensis IgG and increased production of IL-10 and IL-17. Because IL-10 is a mediator of susceptibility to Leishmania infection, we blocked IL-10 signalling in neutrophil-depleted mice using anti-IL-10R. Interestingly, inhibition of IL-10 signalling abrogated the increase in parasite loads observed in neutrophil-depleted mice, suggesting that parasite proliferation is at least partially mediated by IL-10. Additionally, we tested the effect of IL-17 in inflammatory macrophages and observed that IL-17 increased arginase activity and favoured parasite growth. Taken together, our data indicate that neutrophils control parasite numbers and limit lesion development during the first week of infection in BALB/c mice.

Keywords: IL-10; Leishmania amazonensis; immune response; neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / blood
  • Arginase / metabolism
  • Female
  • Immunoglobulin G / blood
  • Interleukin-10 / metabolism
  • Interleukin-17 / metabolism
  • Kinetics
  • Leishmania mexicana / growth & development*
  • Leishmania mexicana / immunology*
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / parasitology*
  • Macrophage Activation
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / parasitology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neutrophil Infiltration
  • Neutrophils / immunology*
  • Parasite Load
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Antibodies, Protozoan
  • Immunoglobulin G
  • Interleukin-17
  • Interleukin-10
  • Arginase