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首页> 外文期刊>Infection and immunity >Infection Stage-Dependent Modulation of Macrophage Activation in Trypanosoma congolense-Resistant and -Susceptible Mice
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Infection Stage-Dependent Modulation of Macrophage Activation in Trypanosoma congolense-Resistant and -Susceptible Mice

机译：锥虫抵抗和易感锥虫的巨噬细胞活化的感染阶段依赖性调制。

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The contribution of cytokines and chemokines to resistance and susceptibility to African trypanosomiasis remains controversial. In the present study, the levels of type I and type II cytokines and of the MCP-1 chemokine were compared during the early and late stages of Trypanosoma congolense infection in susceptible BALB/c and resistant C57BL/6 mice. Moreover, the status of macrophage activation was compared in these animals by analyzing the inducible nitric oxide synthase-arginase balance, tumor necrosis factor secretion, and expression of the FIZZ1 and YM genes. Data show that changing from a predominant type I cytokine environment in the early stage of infection to a predominant type II cytokine environment and an enhanced MCP-1 secretion in the late stage of infection correlates with resistance to T. congolense. Concomitantly, macrophage activation evolves from a classical to a predominant alternative phenotype. We further confirmed that the simultaneous occurrence of type I/type II cytokines in the early stage of infection in susceptible BALB/c mice, reflected by the presence of macrophages exhibiting a mixed classical/alternative activation phenotype, is associated with uncontrolled parasite growth and early death. Interleukin-4 (IL-4) and IL-13 signaling did not influence the susceptibility of BALB/c mice to T. congolense infection and interestingly were not the main trigger to alternative macrophage activation. In T. congolense-resistant C57BL/6 mice, our results corroborated the induction of FIZZ1 and YM gene expressions with the alternative pathway of macrophage activation. In susceptible BALB/c mice, however, YM but not FIZZ1 induction reflected the emergence of alternatively activated macrophages. Hence, the FIZZ1 and YM genes may be useful markers to discriminate between distinct populations of alternatively activated macrophages.
机译：细胞因子和趋化因子对非洲锥虫病的抵抗力和敏感性的贡献仍然存在争议。在本研究中，比较了易感BALB / c和耐药性C57BL / 6的锥虫锥虫感染的早期和晚期，I型和II型细胞因子以及MCP-1趋化因子的水平。老鼠。此外，通过分析诱导型一氧化氮合酶-精氨酸酶的平衡，肿瘤坏死因子的分泌以及FIZZ1和YM基因的表达，比较了这些动物中巨噬细胞活化的状态。数据显示，从感染初期的主要I型细胞因子环境转变为感染初期的II型主要细胞因子环境以及感染后期MCP-1分泌增强与对 T的抵抗力相关。 congolense 。伴随地，巨噬细胞激活从经典表型演变为主要的替代表型。我们进一步证实，易感的BALB / c小鼠在感染早期同时发生I型/ II型细胞因子，反映出巨噬细胞表现出经典的/替代的活化表型，这与寄生虫生长不受控制和早期感染有关。死亡。白介素-4（IL-4）和IL-13信号传导不影响BALB / c小鼠对 T的敏感性。 conogense 感染并不是引起巨噬细胞替代激活的主要诱因。在 T中。 ，我们的结果证实了巨噬细胞活化的替代途径可以诱导FIZZ1和YM基因表达的诱导。然而，在易感的BALB / c小鼠中，YM而非FIZZ1诱导反映了交替激活的巨噬细胞的出现。因此，FIZZ1和YM基因可能是有用的标记，以区分交替激活的巨噬细胞的不同群体。

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