Scientific Publications by FDA Staff

Science 2008 Aug 15;321(5891):970-4

In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies.

Peters NC, Egen JG, Secundino N, Debrabant A, Kimblin N, Kamhawi S, Lawyer P, Fay MP, Germain RN, Sacks D

Egen, JG, NIAID, Immunol Lab, Bldg 10, Bethesda, MD 20892 USA NIAID, Immunol Lab, Bethesda, MD 20892 USA NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA US FDA, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA NIAID, Biostat Res Branch, Bethesda, MD 20892 USA

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.