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Science 15 August 2008:
Vol. 321. no. 5891, pp. 970 - 974
DOI: 10.1126/science.1159194
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Reports

In Vivo Imaging Reveals an Essential Role for Neutrophils in Leishmaniasis Transmitted by Sand Flies

Nathan C. Peters,1* Jackson G. Egen,2*{dagger} Nagila Secundino,1 Alain Debrabant,3 Nicola Kimblin,1 Shaden Kamhawi,1 Phillip Lawyer,1 Michael P. Fay,4 Ronald N. Germain,2{ddagger} David Sacks1{dagger}{ddagger}

Infection with the obligate intracellular protozoan Leishmania is thought to be initiated by direct parasitization of macrophages, but the early events following transmission to the skin by vector sand flies have been difficult to examine directly. Using dynamic intravital microscopy and flow cytometry, we observed a rapid and sustained neutrophilic infiltrate at localized sand fly bite sites. Invading neutrophils efficiently captured Leishmania major (L.m.) parasites early after sand fly transmission or needle inoculation, but phagocytosed L.m. remained viable and infected neutrophils efficiently initiated infection. Furthermore, neutrophil depletion reduced, rather than enhanced, the ability of parasites to establish productive infections. Thus, L.m. appears to have evolved to both evade and exploit the innate host response to sand fly bite in order to establish and promote disease.

1 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
2 Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
3 Laboratory of Bacterial, Parasitic, and Unconventional Agents, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA.
4 Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.

* These authors contributed equally to this work.

{ddagger} These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: dsacks{at}nih.gov (D.S.); jegen{at}niaid.nih.gov (J.G.E.)

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Science. ISSN 0036-8075 (print), 1095-9203 (online)