Popi Ana Flavia, Godoy Luiz Claudio, Xander Patricia, Lopes Jose Daniel, Mariano Mario
Department of Microbiology, Immunology and Parasitology, Universidade Federal de São Paulo, Rua Botucatu 862, São Paulo, SP, Brazil.
Microbes Infect. 2008 Jun;10(7):817-24. doi: 10.1016/j.micinf.2008.04.012. Epub 2008 Apr 30.
Protective immunity in paracoccidioidomycosis is mainly mediated by cellular immunity. The role of B cells in this disease, in particular B-1 cells, is poorly understood. The aim of this study was to characterize the participation of B-1 cells in resistance or susceptibility of BALB/c and BALB/Xid mice to P. brasiliensis (Pb) pulmonary infection. BALB/Xid, which lacks B-1 cells, exhibited higher resistance to infection when compared with BALB/c mice. However, adoptive transfer of B-1 cells to BALB/Xid mice drastically increased the susceptibility of these animals to Pb infection. The fungal burden in BALB/c and B-1-reconstituted BALB/Xid was significantly higher as compared to BALB/Xid strain. Compact, well-organized granulomas were observed in the lungs of BALB/Xid mice, whereas large lesions with necrotic center with a plethora of fungi developed in BALB/c mice. It was also shown that B-1 cells impair phagocytosis of Pb by macrophages in vitro via secretion of IL-10, which was increased upon stimulation with a purified Pb antigen, gp43. Finally, in vivo blockade of IL-10 led to a better control of infection by the highly susceptible B10.A mouse. These findings suggest that B-1 cells play a major role in resistance/susceptibility to Pb infection in murine models, most likely via production of IL-10.
副球孢子菌病的保护性免疫主要由细胞免疫介导。B细胞,尤其是B-1细胞在该疾病中的作用尚不清楚。本研究的目的是描述B-1细胞在BALB/c和BALB/Xid小鼠对巴西副球孢子菌(Pb)肺部感染的抗性或易感性中的参与情况。缺乏B-1细胞的BALB/Xid与BALB/c小鼠相比,对感染表现出更高的抗性。然而,将B-1细胞过继转移到BALB/Xid小鼠中,极大地增加了这些动物对Pb感染的易感性。与BALB/Xid品系相比,BALB/c和B-1细胞重建的BALB/Xid中的真菌负荷显著更高。在BALB/Xid小鼠的肺中观察到紧密、组织良好的肉芽肿,而在BALB/c小鼠中则出现了带有坏死中心且有大量真菌的大病变。还表明,B-1细胞在体外通过分泌IL-10损害巨噬细胞对Pb的吞噬作用,在用纯化的Pb抗原gp43刺激后,IL-10分泌增加。最后,体内阻断IL-10导致高度易感的B10.A小鼠对感染的控制更好。这些发现表明,B-1细胞在小鼠模型中对Pb感染的抗性/易感性中起主要作用,很可能是通过产生IL-10。