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Infection and Immunity, February 2008, p. 532-541, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01388-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Neutrophils Contribute to Development of a Protective Immune Response during Onset of Infection with Leishmania donovani

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom,¹ WHO Immunology Research and Training Center, Department of Biochemistry, University of Lausanne, Epalinges, Switzerland²

Received 16 October 2007/ Returned for modification 10 November 2007/ Accepted 21 November 2007

Neutrophils are key components of the inflammatory response and as such contribute to the killing of microorganisms. In addition, recent evidence suggests their involvement in the development of the immune response. The role of neutrophils during the first weeks post-infection with Leishmania donovani was investigated in this study. When L. donovani-infected mice were selectively depleted of neutrophils with the NIMP-R14 monoclonal antibody, a significant increase in parasite numbers was observed in the spleen and bone marrow and to a lesser extent in the liver. Increased susceptibility was associated with enhanced splenomegally, a delay in the maturation of hepatic granulomas, and a decrease in inducible nitric oxide synthase expression within granulomas. In the spleen, neutrophil depletion was associated with a significant increase in interleukin 4 (IL-4) and IL-10 levels and reduced gamma interferon secretion by CD4⁺ and CD8⁺ T cells. Increased production of serum IL-4 and IL-10 and higher levels of Leishmania-specific immunoglobulin G1 (IgG1) versus IgG2a revealed the preferential induction of Th2 responses in neutrophil-depleted mice. Altogether, these data suggest a critical role for neutrophils in the early protective response against L. donovani, both as effector cells involved in the killing of the parasites and as significant players influencing the development of a protective Th1 immune response.

Published ahead of print on 3 December 2007.

Editor: W. A. Petri, Jr.