Departmento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Av. Bandeirantes 3900, Ribeirão Preto, 14049-900, Brazil.
Mycopathologia. 2013 Aug;176(1-2):1-10. doi: 10.1007/s11046-013-9671-y. Epub 2013 Jun 14.
Paracoccidioidomycosis (PCM) is a chronic granulomatous disease caused by the thermally dimorphic fungus Paracoccidioides brasiliensis. T helper 1 (Th1)-mediated immunity is primarily responsible for acquired resistance during P. brasiliensis infection. On the contrary, the susceptibility is associated with occurrence of type-2 immunity (Th2), which is characterized by IL-4 release, B cell activation, and production of antibodies. Although antibodies are frequently associated with severe PCM, it is not clear whether they contribute to susceptibility or merely constitute a marker of infection stage. Here, we assessed the function of B cells during experimental P. brasiliensis infection in mice, and our results showed that B cell-knockout (B(KO)) mice are more susceptible than their wild-type littermate controls (C57BL/6, WT). The B(KO) mice showed higher mortality rate, increased number of colony-forming units in the lungs, and larger granulomas than WT mice. In the absence of B cells, we observed high levels of IL-10, whereas IFN-γ, TNF-α, and IL-4 levels were similar between both groups. Finally, we showed that transference of WT immune serum to B(KO) mice resulted in diminished infiltration of inflammatory cells and better organization of the pulmonary granulomas. Taken together, these data suggest that B cells are effectively involved in the control of P. brasiliensis growth and organization of the granulomatous lesions observed during the experimental PCM.
球孢子菌病(PCM)是一种由热双相真菌巴西副球孢子菌引起的慢性肉芽肿性疾病。辅助性 T 细胞 1(Th1)介导的免疫是巴西副球孢子菌感染获得性抗性的主要原因。相反,易感性与 2 型免疫(Th2)的发生有关,其特征是释放白细胞介素 4(IL-4)、B 细胞活化和产生抗体。尽管抗体通常与严重的 PCM 相关,但尚不清楚它们是否有助于易感性,还是仅仅构成感染阶段的标志物。在这里,我们评估了 B 细胞在实验性巴西副球孢子菌感染中的功能,结果表明 B 细胞敲除(B(KO))小鼠比其野生型同窝对照(C57BL/6,WT)更易感。B(KO)小鼠的死亡率更高,肺部菌落形成单位数量增加,肉芽肿也比 WT 小鼠大。在没有 B 细胞的情况下,我们观察到高水平的白细胞介素 10(IL-10),而 IFN-γ、TNF-α 和 IL-4 水平在两组之间相似。最后,我们表明,将 WT 免疫血清转移到 B(KO)小鼠中导致炎症细胞浸润减少和肺部肉芽肿更好地组织化。综上所述,这些数据表明 B 细胞有效参与了巴西副球孢子菌生长的控制和实验性 PCM 中观察到的肉芽肿病变的组织。