Neutrophils contribute to the development of a protective immune response 1 during the onset of infection with Leishmania donovani

1 2 Neutrophils are key components of the inflammatory response and as such contribute to the 3 killing of microorganisms. In addition, recent evidence suggests their involvement in the 4 development of the immune response. The role of neutrophils during the first weeks post 5 infection with Leishmania donovani was investigated in this study. When L. donovani6 infected mice were selectively depleted of neutrophils with the NIMP-R14 mAb, a 7 significant increase of parasite numbers was observed in the spleen and bone marrow, and to 8 a lesser extent in the liver. Increased susceptibility was associated with enhanced 9 splenomegally, a delay in the maturation of hepatic granulomas and a decrease in iNOS 10 expression within granulomas. In the spleen, neutrophil depletion was associated with a 11 significant increase in IL-4 and IL-10 levels, and reduced IFN-γ secretion by CD4 + and CD8 + 12 T cells. Increased production of serum IL-4 and IL-10 and higher levels of Leishmania13 specific IgG1versus IgG2a, revealed the preferential induction of a Th2 responses in 14 neutrophil-depleted mice. Altogether, these data suggest a critical role for neutrophils in the 15 early protective response against L. donovani, both as effector cells involved in the killing of 16 the parasites, and as significant players influencing the development of a protective Th1 17 immune response. 18 AC CE PT ED