Silva J S, Aliberti J C, Martins G A, Souza M A, Souto J T, Pádua M A
Departamento de Parasitologia, Microbiologia e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brasil.
Braz J Med Biol Res. 1998 Jan;31(1):111-5. doi: 10.1590/s0100-879x1998000100014.
Host resistance to Trypanosoma cruzi infection is dependent on both natural and acquired immune responses. During the early acute phase of infection in mice, natural killer (NK) cell-derived IFN-gamma is involved in controlling intracellular parasite replication, mainly through the induction of nitric oxide biosynthesis by activated macrophages. We have shown that IL-12, a powerful inducer of IFN-gamma production by NK cells, is synthesized soon after trypomastigote-macrophage interaction. The role of IL-12 in the control of T. cruzi infection in vivo was determined by treating infected mice with anti-IL-12 monoclonal antibody (mAb) and analyzing both parasitemia and mortality during the acute phase of infection. The anti-IL-12 mAb-treated mice had higher levels of parasitemia and mortality compared to control mice. Also, treatment of infected mice with mAb specific for IFN-gamma or TNF-alpha inhibited the protective effect of exogenous IL-12. On the other hand, TGF-beta and IL-10 produced by infected macrophages inhibited the induction and effects of IL-12. Therefore, while IL-12, TNF-alpha and IFN-gamma correlate with resistance to T. cruzi infection, TGF-beta and IL-10 promote susceptibility. These results provide support for a role of innate immunity in the control of T. cruzi infection. In addition to its protective role, IL-12 may also be involved in the modulation of T. cruzi-induced myocarditis, since treatment of infected mice with IL-12 or anti-IL-12 mAb leads to an enhanced or decreased inflammatory infiltrate in the heart, respectively. Understanding the role of the cytokines produced during the acute phase of T. cruzi infection and their involvement in protection and pathogenesis would be essential to devise new vaccines or therapies.
宿主对克氏锥虫感染的抵抗力取决于天然免疫和获得性免疫反应。在小鼠感染的早期急性期，自然杀伤（NK）细胞衍生的干扰素-γ参与控制细胞内寄生虫的复制，主要是通过激活的巨噬细胞诱导一氧化氮的生物合成。我们已经表明，白细胞介素-12（IL-12）是NK细胞产生干扰素-γ的强大诱导剂，在锥鞭毛体与巨噬细胞相互作用后很快就会合成。通过用抗IL-12单克隆抗体（mAb）治疗感染的小鼠，并分析感染急性期的寄生虫血症和死亡率，确定了IL-12在体内控制克氏锥虫感染中的作用。与对照小鼠相比，用抗IL-12 mAb治疗的小鼠寄生虫血症水平和死亡率更高。此外，用针对干扰素-γ或肿瘤坏死因子-α（TNF-α）的mAb治疗感染的小鼠会抑制外源性IL-12的保护作用。另一方面，感染的巨噬细胞产生的转化生长因子-β（TGF-β）和IL-10会抑制IL-12的诱导及其作用。因此，虽然IL-12、TNF-α和干扰素-γ与对克氏锥虫感染的抵抗力相关，但TGF-β和IL-10会促进易感性。这些结果为先天免疫在控制克氏锥虫感染中的作用提供了支持。除了其保护作用外，IL-12还可能参与克氏锥虫诱导的心肌炎的调节，因为用IL-12或抗IL-12 mAb治疗感染的小鼠分别会导致心脏炎症浸润增加或减少。了解克氏锥虫感染急性期产生的细胞因子的作用及其在保护和发病机制中的参与对于设计新的疫苗或疗法至关重要。
