Both the Fas Ligand and Inducible Nitric Oxide Synthase Are Needed for Control of Parasite Replication within Lesions in Mice Infected with Leishmania major whereas the Contribution of Tumor Necrosis Factor Is Minimal
Both the Fas Ligand and Inducible Nitric Oxide Synthase Are Needed for Control of Parasite Replication within Lesions in Mice Infected with Leishmania major whereas the Contribution of Tumor Necrosis Factor Is Minimal
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Fas配体和诱导型一氧化氮合酶都需要控制感染大型利什曼原虫的小鼠病变内的寄生虫复制，而肿瘤坏死因子的贡献却很小
作者：
R. Chakour;R. Guler;Mélanie Bugnon;C. Allenbach;I. Garcia;J. Mauël;J. Louis;F. Tacchini
C57 BL/6小鼠感染大型利什曼原虫后，出现一个小的病变，并能自发愈合。对感染的抗性与产生γ干扰素（IFN-γ）和肿瘤坏死因子（TNF）的CD 4 + Th 1细胞的发展相关，所述γ干扰素和TNF协同活化巨噬细胞至其杀微生物状态。我们在这里显示，缺乏TNF和Fas配体（FasL）的C57 BL/6小鼠（gld TNF−/−小鼠）感染L. major既没有解决他们的病变，也没有控制利什曼原虫的复制，尽管发展了强烈的Th 1应答。在TNF−/−、gld TNF−/−和gld小鼠的病变中检测到了类似的诱导型一氧化氮合酶（iNOS）活性，但只有gld和gld TNF−/−小鼠未能控制寄生虫复制。在gld小鼠中寄生虫数量很高，在gld TNF-/-小鼠中甚至更高，这表明，除了iNOS，Fas/FasL途径是成功控制寄生虫复制所必需的，而TNF对这一过程只起了很小的作用。此外，FasL显示出与IFN-γ协同诱导感染L.主要是体外。有趣的是，TNF-/-小鼠在整个感染过程中保持了较大的病变大小，尽管能够在很大程度上控制寄生虫数量。因此，IFN-γ、FasL和iNOS似乎对于完全控制寄生虫复制是必不可少的，而TNF的贡献在控制寄生虫接种部位的炎症方面更重要。
ABSTRACT Following infection with the protozoan parasite Leishmania major, C57BL/6 mice develop a small lesion that heals spontaneously. Resistance to infection is associated with the development of CD4+ Th1 cells producing gamma interferon (IFN-γ) and tumor necrosis factor (TNF), which synergize in activating macrophages to their microbicidal state. We show here that C57BL/6 mice lacking both TNF and Fas ligand (FasL) (gld TNF−/− mice) infected with L. major neither resolved their lesions nor controlled Leishmania replication despite the development of a strong Th1 response. Comparable inducible nitric oxide synthase (iNOS) activities were detected in lesions of TNF−/−, gld TNF−/−, and gld mice, but only gld and gld TNF−/− mice failed to control parasite replication. Parasite numbers were high in gld mice and even more elevated in gld TNF−/− mice, suggesting that, in addition to iNOS, the Fas/FasL pathway is required for successful control of parasite replication and that TNF contributes only a small part to this process. Furthermore, FasL was shown to synergize with IFN-γ for the induction of leishmanicidal activity within macrophages infected with L. major in vitro. Interestingly, TNF−/− mice maintained large lesion size throughout infection, despite being able to largely control parasite numbers. Thus, IFN-γ, FasL, and iNOS appear to be essential for the complete control of parasite replication, while the contribution of TNF is more important in controlling inflammation at the site of parasite inoculation.
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影响因子：
4.4
作者：
S. Kanaly;M. Nashleanas;B. Hondowicz;P. Scott
通讯作者：
S. Kanaly;M. Nashleanas;B. Hondowicz;P. Scott
控制缺乏 TNF 受体的小鼠的利什曼原虫主要感染。
DOI：
--
发表时间：
1998
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Nashleanas,M;Kanaly,S;Scott,P
通讯作者：
Scott,P
影响因子：
32.4
作者：
LYNCH, DH;WATSON, ML;SELDIN, MF
通讯作者：
SELDIN, MF
缺乏 TNF 受体 p55 的小鼠无法消除由大型利什曼原虫感染引起的病变，但可以控制寄生虫的复制。
DOI：
--
发表时间：
1996
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Vieira,LQ;Goldschmidt,M;Nashleanas,M;Pfeffer,K;Mak,T;Scott,P
通讯作者：
Scott,P
影响因子：
32.4
作者：
Beebe, AM;Mauze, S;Coffman, RL
通讯作者：
Coffman, RL