Peters Nathan C, Egen Jackson G, Secundino Nagila, Debrabant Alain, Kimblin Nicola, Kamhawi Shaden, Lawyer Phillip, Fay Michael P, Germain Ronald N, Sacks David
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Science. 2008 Aug 15;321(5891):970-4. 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.
专性细胞内原生动物利什曼原虫的感染被认为是由巨噬细胞的直接寄生引发的,但沙蝇将其传播至皮肤后的早期事件一直难以直接进行检测。利用动态活体显微镜和流式细胞术,我们在沙蝇叮咬的局部位点观察到了快速且持续的嗜中性粒细胞浸润。在沙蝇传播或针刺接种后不久,侵入的嗜中性粒细胞就能有效地捕获大型利什曼原虫(L.m.)寄生虫,但被吞噬的L.m.仍保持存活,且受感染的嗜中性粒细胞能有效地引发感染。此外,嗜中性粒细胞的耗竭降低而非增强了寄生虫建立有效感染的能力。因此,L.m.似乎已经进化到既能逃避又能利用宿主对沙蝇叮咬的固有反应,从而建立并促进疾病发展。