Interferon-γ and nitric oxide in combination with antibodies are key protective host immune factors during Trypanosoma congolense Tc13 infections
Interferon-γ and nitric oxide in combination with antibodies are key protective host immune factors during Trypanosoma congolense Tc13 infections
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DOI：
10.1086/503808
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发表时间：
2006-06-01
影响因子：
6.4
通讯作者：
De Baetselier, P
中科院分区：
文献类型：
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作者：
Magez, S;Radwanska, M;De Baetselier, P
使用几种基因缺陷小鼠品系分析慢性刚果锥虫锥虫病的控制。首先，使用干扰素（IFN）-γ受体（IFN-γ-R）缺陷型小鼠来显示IFN-γ介导的免疫激活对于寄生虫血症控制至关重要。其次，在主要组织相容性复合体（MHC）II类缺陷小鼠中的感染表明，这种分子是IFN-γ和随后的肿瘤坏死因子（TNF）产生的起始所必需的。在IFN-γ-R信号传导的下游，发生诱导型NO合酶（iNOS）依赖性锥虫杀伤，如iNOS缺陷小鼠的过敏表型所示。除了促炎反应外，B细胞，更具体地说，免疫球蛋白（IG）G抗体对寄生虫杀伤至关重要。因此，在B细胞缺陷型小鼠中寄生虫血症控制被消除，而IgM缺陷型小鼠与野生型小鼠一样有效地控制感染。此外，具有正常IgM应答但受损IgG 2a/3应答的脾切除小鼠不能控制T。刚果感染。总的来说，这些结果表明，宿主对T。刚果红细胞主要依赖于促炎介质/效应物IFN-γ、TNF和NO以及抗寄生虫IgG的联合作用。
The control of chronic Trypanosoma congolense trypanosomiasis was analyzed using several gene-deficient mouse strains. First, interferon (IFN)-gamma receptor ( IFN-gamma-R)-deficient mice were used to show that IFN-gamma-mediated immune activation is crucial for parasitemia control. Second, infections in major histocompatibility complex (MHC) class II-deficient mice indicate that this molecule is needed for initiation of IFN-gamma and subsequent tumor necrosis factor (TNF) production. Downstream of IFN-gamma-R signaling, inducible NO synthase (iNOS)-dependent trypanosome killing occurs, as is shown by the hypersusceptible phenotype of iNOS-deficient mice. Besides proinflammatory responses, B cells and, more specifically, immunoglobulin (Ig) G antibodies are crucial for parasite killing. Hence, parasitemia control is abolished in B cell-deficient mice, whereas IgM-deficient mice control the infection as efficiently as do wild-type mice. In addition, splenectomized mice that have a normal IgM response but an impaired IgG2a/3 response fail to control T. congolense infection. Collectively, these results suggest that host protective immunity against T. congolense is critically dependent on the combined action of the proinflammatory mediators/effectors IFN-gamma, TNF, and NO and antiparasite IgGs.