Allen Holly L, Deepe George S
Division of Infectious Diseases, Veterans Affairs Hospital, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
J Immunol. 2006 Aug 1;177(3):1763-71. doi: 10.4049/jimmunol.177.3.1763.
The fungus, Histoplasma capsulatum, produces a persistent infection. Reactivation histoplasmosis is largely a result of impaired immunity, but the perturbations associated with escape of the fungus from host defenses remain ill-defined. We analyzed a murine model of reactivation to elucidate the host defects that permit reactivation. C57BL/6 mice were infected intranasally and, 42 days later, they were depleted of CD4(+) and CD8(+) cells. Elimination of these cells, but not either alone, produced a persistent infection over several weeks. Neutralization of IFN-gamma, TNF-alpha, or both did not induce reactivation. Endogenous IL-10 exacerbated reactivation. Depletion of T cells in B cell(-/-) mice induced a markedly higher burden in organs when compared with wild type. However, the infection remained persistent. Elimination of CD4(+) cells alone or neutralization of cytokines increased the fungal load. The persistent infection was not dependent on gammadelta T cells or NK cells. Elimination of Thy-1.2(+) cells in mice given mAb to CD4 and CD8 transformed reactivation into a progressive, lethal infection in B cell(-/-) and wild-type mice, but the tempo of progression was accelerated in the former. The data reveal the complex control by the host to prevent reactivation of this fungus.
荚膜组织胞浆菌可引发持续性感染。复发性组织胞浆菌病很大程度上是免疫功能受损的结果，但与真菌逃避宿主防御相关的干扰因素仍不明确。我们分析了复发性感染的小鼠模型，以阐明允许感染复发的宿主缺陷。将C57BL/6小鼠经鼻感染，42天后，清除其CD4(+)和CD8(+)细胞。清除这些细胞（而非单独清除其中一种）会导致数周的持续性感染。中和IFN-γ、TNF-α或两者均不能诱导感染复发。内源性IL-10会加剧感染复发。与野生型相比，B细胞缺陷（B cell(-/-)）小鼠中T细胞的清除在器官中诱导出明显更高的菌负荷。然而，感染仍持续存在。单独清除CD4(+)细胞或中和细胞因子会增加真菌负荷。持续性感染不依赖于γδ T细胞或NK细胞。在给予抗CD4和抗CD8单克隆抗体的小鼠中清除Thy-1.2(+)细胞，会使B细胞缺陷（B cell(-/-)）小鼠和野生型小鼠的复发性感染转变为进行性致死性感染，但前者的进展速度更快。这些数据揭示了宿主为防止这种真菌复发而进行的复杂调控。
