Resistance to acute babesiosis is associated with interleukin-12- and gamma interferon-mediated responses and requires macrophages and natural killer cells
Resistance to acute babesiosis is associated with interleukin-12- and gamma interferon-mediated responses and requires macrophages and natural killer cells
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DOI：
10.1128/iai.71.4.2002-2008.2003
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发表时间：
2003-04-01
影响因子：
3.1
通讯作者：
Persing, DH
中科院分区：
文献类型：
--
作者：
Aguilar-Delfin, I;Wettstein, PJ;Persing, DH
我们检测了细胞因子γ干扰素（ifn - γ）和白细胞介素-12 （IL-12）在急性巴贝斯虫病WA1巴贝斯虫模型中的作用。将ifn - γ介导的基因缺陷小鼠（IFNGR2KO小鼠）和il -12介导的基因缺陷小鼠（Stat4KO小鼠）感染WAI巴贝虫，观察其感染过程和细胞因子反应。接种寄生虫24 h后血清中ifn - γ和IL-12水平升高。在IFNGR2KO和Stat-4KO小鼠中观察到的增强易感性表明，早期IL-12和ifn - γ介导的反应参与了对急性巴贝斯虫病的保护。抗性似乎与一氧化氮（NO）产生的增加有关。为了评估不同细胞亚群对抵抗寄生虫的贡献，我们还研究了缺乏B细胞、CD4(+) T细胞、NK细胞和巨噬细胞的小鼠。B淋巴细胞或CD4(+) T淋巴细胞基因缺陷的小鼠能够产生与免疫充足小鼠相当的保护反应。相反，体内巨噬细胞或NK细胞的消耗导致对感染的易感性升高。我们的观察结果表明，巨噬细胞和NK细胞可能通过早期产生IL-12和ifn - γ以及诱导巨噬细胞衍生的效应分子（如NO）介导了对致病性巴贝斯虫WA1的保护反应的关键部分。
We examined the role of the cytokines gamma interferon (IFN-gamma) and interleukin-12 (IL-12) in the model of acute babesiosis with the WA1 Babesia. Mice genetically deficient in IFN-gamma-mediated responses (IFNGR2KO mice) and IL-12-mediated responses (Stat4KO mice) were infected with the WAI Babesia, and observations were made on the course of infection and cytokine responses. Levels of IFN-gamma and IL-12 in serum increased 24 h after parasite inoculation. The augmented susceptibility observed in IFNGR2KO and Stat-4KO mice suggests that the early IL-12- and IFN-gamma-mediated responses-are involved in protection against acute babesiosis. Resistance appears to correlate with an increase in nitric oxide (NO) production. In order to assess the contribution of different cell subsets to resistance against the parasite, we also studied mice lacking B cells, CD4(+) T cells, NK cells, and macrophages. Mice genetically deficient in B lymphocytes or CD4(+) T lymphocytes were able to mount protective responses comparable to those of immunosufficient mice. In contrast, in vivo depletion of macrophages or NK cells resulted in elevated susceptibility to the infection. Our observations suggest that a crucial part of the response that protects from the pathogenic Babesia WA1 is mediated by macrophages and NK cells, probably through early production of IL-12 and IFN-gamma, and induction of macrophage-derived effector molecules like NO.