Site-Dependent Recruitment of Inflammatory Cells Determines the Effective Dose of Leishmania major
Site-Dependent Recruitment of Inflammatory Cells Determines the Effective Dose of Leishmania major
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DOI：
10.1128/iai.01600-13
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发表时间：
2014-07-01
影响因子：
3.1
通讯作者：
Peters, Nathan C.
中科院分区：
文献类型：
--
作者：
Ribeiro-Gomes, Flavia L.;Roma, Eric Henrique;Peters, Nathan C.
已证明通过针头接种病原体的途径会影响感染的结果。采用针接种专性细胞内寄生虫硕大利什曼原虫，其在皮内（i.d.）通过被感染的白蛉叮咬沉积寄生虫，我们鉴定了i.d.耳皮下接种（s.c.）足垫接种或腹膜腔接种（腹膜内[i.p.]接种）。不同部位的感染起始与不同的吞噬细胞群有关。中性粒细胞是i.d.后的主要感染细胞，但不是s.c.。或i.p.，接种。接种的耳朵真皮导致更高的总的频率和感染的中性粒细胞比接种的足垫，这些较高的频率与早期寄生虫负荷增加10倍。在没有中性粒细胞的情况下接种耳后，其他细胞类型的寄生虫吞噬作用没有增加，并且很少有寄生虫能够建立感染。总感染CD 11b（+）人群中感染中性粒细胞的频率高于总CD 11b（+）人群中总中性粒细胞的频率，表明中性粒细胞在感染细胞中的比例过高。使用ID接种以模拟白蛉传播寄生虫相对于s.c.或i.p.接种，包括感染细胞的表型和建立感染的寄生虫的数量。在真皮中开始的媒介传播的感染可能涉及对这种独特微环境的适应。阻止或改变这一初始步骤对感染有重大影响。
The route of pathogen inoculation by needle has been shown to influence the outcome of infection. Employing needle inoculation of the obligately intracellular parasite Leishmania major, which is transmitted in nature following intradermal (i.d.) deposition of parasites by the bite of an infected sand fly, we identified differences in the preexisting and acute cellular responses in mice following i.d. inoculation of the ear, subcutaneous (s.c.) inoculation of the footpad, or inoculation of the peritoneal cavity (intraperitoneal [i.p.] inoculation). Initiation of infection at different sites was associated with different phagocytic populations. Neutrophils were the dominant infected cells following i.d., but not s.c. or i.p., inoculation. Inoculation of the ear dermis resulted in higher frequencies of total and infected neutrophils than inoculation of the footpad, and these higher frequencies were associated with a 10-fold increase in early parasite loads. Following inoculation of the ear in the absence of neutrophils, parasite phagocytosis by other cell types did not increase, and fewer parasites were able to establish infection. The frequency of infected neutrophils within the total infected CD11b(+) population was higher than the frequency of total neutrophils within the total CD11b(+) population, demonstrating that neutrophils are overrepresented as a proportion of infected cells. Employing i.d. inoculation to model sand fly transmission of parasites has significant consequences for infection outcome relative to that of s.c. or i.p. inoculation, including the phenotype of infected cells and the number of parasites that establish infection. Vector-borne infections initiated in the dermis likely involve adaptations to this unique microenvironment. Bypassing or altering this initial step has significant consequences for infection.