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

• Published in: Science (American Association for the Advancement of Science) Vol. 321; no. 5891; pp. 970 - 974
• Main Authors: Peters, Nathan C, Egen, Jackson G, Secundino, Nagila, Debrabant, Alain, Kimblin, Nicola, Kamhawi, Shaden, Lawyer, Phillip, Fay, Michael P, Germain, Ronald N, Sacks, David
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 15-08-2008; The American Association for the Advancement of Science
• Subjects: Animals; Apoptosis; Biological and medical sciences; Biomedical research; Bites and stings; Cell Movement; Flow Cytometry; Host-Parasite Interactions; Human protozoal diseases; Infections; Infectious diseases; Inoculation; Insect Bites and Stings; Insect Vectors - parasitology; Insects; Leishmania major; Leishmania major - immunology; Leishmania major - physiology; Leishmaniasis, Cutaneous - immunology; Leishmaniasis, Cutaneous - parasitology; Leishmaniasis, Cutaneous - transmission; Leshmaniasis; Macrophages; Macrophages - parasitology; Medical imaging; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy; Neutrophil Infiltration; Neutrophils; Neutrophils - immunology; Neutrophils - parasitology; Neutrophils - physiology; Parasite hosts; Parasites; Parasitic diseases; Parasitology; Phagocytes; Phagocytosis; Phlebotomus - parasitology; Protozoal diseases; Skin - immunology; Skin - parasitology; Infection; Flow cytometry; In vivo; Protozoal disease; Microscopy; Transmission; Medical imagery; Parasitosis; Leishmaniasis; Neutrophil
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1159194

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.