title: In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies.
abstract: 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.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Peters
authors.forename: Jackson G
authors.initials: JG
authors.lastname: Egen
authors.forename: Nagila
authors.initials: N
authors.lastname: Secundino
authors.forename: Alain
authors.initials: A
authors.lastname: Debrabant
authors.forename: Nicola
authors.initials: N
authors.lastname: Kimblin
authors.forename: Shaden
authors.initials: S
authors.lastname: Kamhawi
authors.forename: Phillip
authors.initials: P
authors.lastname: Lawyer
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fay
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Germain
authors.forename: David
authors.initials: D
authors.lastname: Sacks
mesh_terms: D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D005434:Flow Cytometry; D006790:Host-Parasite Interactions; D007299:Insect Bites and Stings; D007303:Insect Vectors / Q000469:parasitology; D018320:Leishmania major / Q000276:immunology / Q000502:physiology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology* / Q000635:transmission; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008853:Microscopy; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology* / Q000469:parasitology* / Q000502:physiology; D010587:Phagocytosis; D010691:Phlebotomus / Q000469:parasitology*; D012867:Skin / Q000276:immunology / Q000469:parasitology