In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies.
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.
Peters
Nathan C
NC
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Egen
Jackson G
JG
Secundino
Nagila
N
Debrabant
Alain
A
Kimblin
Nicola
N
Kamhawi
Shaden
S
Lawyer
Phillip
P
Fay
Michael P
MP
Germain
Ronald N
RN
Sacks
David
D
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