Type I IFNs stimulate nitric oxide production and resistance to Trypanosoma cruzi infection
Type I IFNs stimulate nitric oxide production and resistance to Trypanosoma cruzi infection
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DOI：
10.4049/jimmunol.177.5.3193
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发表时间：
2006-09-01
影响因子：
4.4
通讯作者：
Abrahamsohn, Ises A.
中科院分区：
文献类型：
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作者：
Costa, Vlaudia M. A.;Torres, Karen C. L.;Abrahamsohn, Ises A.
研究了I型干扰素（IFN-I）在一氧化氮（NO）产生和抗克氏锥虫感染中的作用。贴壁细胞从腹腔感染途径感染的小鼠腹腔获得产生NO和IFN-I。通过用抗IFN-α β或抗TNF-α Ab处理，这些细胞的NO合成被部分抑制。与敏感的BALB/c小鼠相比，寄生虫感染的抗性C57 BL/6小鼠的腹膜细胞产生更多的NO（2倍），IFN-I（10倍）和TNF-α（3.5倍）。在感染后期，在C57 BL/6小鼠中，在来自感染8天的小鼠的脾细胞（SC）培养物中测量的IFN-I水平高于感染的BALB/c小鼠，并且用抗IFN-α β Ab处理培养物减少NO产生。两种小鼠品系之间SC产生IFN-γ或IL-10没有差异; IL-4检测不到。用IFN-I治疗C57 BL/6小鼠降低了感染急性期的寄生虫血症水平。与对照129 Sv小鼠相比，剥夺IFN-alpha β R基因的小鼠在急性期的寄生虫血症水平高出3倍。在缺乏IFN-α β信号的小鼠中，腹腔巨噬细胞和SC产生的NO减少，而巨噬细胞的寄生比对照野生型小鼠更重。我们的结论是，IFN-I共刺激T. Cruzi感染，这有助于更好地控制抗性小鼠中的寄生虫血症。
The participation of type I IFNs (IFN-I) in NO production and resistance to Trypanosoma cruzi infection was investigated. Adherent cells obtained from the peritoneal cavity of mice infected by the i.p. route produced NO and IFN-I. Synthesis of NO by these cells was partially inhibited by treatment with anti-IFN-alpha beta or anti-TNF-alpha Abs. Compared with susceptible BALB/c mice, peritoneal cells from parasite-infected resistant C57BL/6 mice produced more NO (2-fold), IFN-I (10-fold), and TNF-alpha (3.5-fold). Later in the infection, IFN-I levels measured in spleen cell (SC) cultures from 8-day infected mice were greater in C57BL/6 than in infected BALB/c mice, and treatment of the cultures with anti-IFN-alpha beta Ab reduced NO production. IFN-gamma or IL-10 production by SCs was not different between the two mouse strains; IL-4 was not detectable. Treatment of C57BL/6 mice with IFN-I reduced parasitemia levels in the acute phase of infection. Mice deprived of the IFN-alpha beta R gene developed 3-fold higher parasitemia levels in the acute phase in comparison with control 129Sv mice. Production of NO by peritoneal macrophages and SCs was reduced in mice that lacked signaling by IFN-alpha beta, whereas parasitism of macrophages was heavier than in control wild-type mice. We conclude that IFN-I costimulate NO synthesis early in T. cruzi infection, which contributes to a better control of the parasitemia in resistant mice.