Cenci E, Mencacci A, Fè d'Ostiani C, Del Sero G, Mosci P, Montagnoli C, Bacci A, Romani L
Microbiology Section, Department of Experimental Medicine, University of Perugia, Italy.
J Infect Dis. 1998 Dec;178(6):1750-60. doi: 10.1086/314493.
The role of cytokine- and T helper (Th)-dependent lung mucosal antifungal immunity in murine invasive pulmonary aspergillosis (IPA) was investigated. Intact or leukopenic DBA/2 mice were resistant or highly susceptible, respectively, to infection caused by multiple intranasal injections of viable Aspergillus fumigatus conidia. Resistance was associated with unimpaired innate antifungal activity of pulmonary phagocytic cells, concomitant with high-level production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-12 and the presence of interstitial lymphocytes producing interferon-gamma and IL-2. Conversely, production of TNF-alpha and IL-12 was down-regulated in highly susceptible mice, which also had defective innate antifungal immunity and high-level production of IL-4 and IL-10 by lung lymphocytes. Resistance was increased in susceptible mice upon local IL-4 or IL-10 neutralization or IL-12 administration. These results indicate that, similar to observations in mice with disseminated aspergillosis, innate and Th1-dependent immunity play an essential role in host defense against IPA.
研究了细胞因子和辅助性T细胞（Th）依赖性肺黏膜抗真菌免疫在小鼠侵袭性肺曲霉病（IPA）中的作用。完整或白细胞减少的DBA/2小鼠分别对多次鼻内注射活的烟曲霉分生孢子引起的感染具有抗性或高度易感性。抗性与肺吞噬细胞未受损的先天性抗真菌活性相关，同时伴有高水平的肿瘤坏死因子（TNF）-α和白细胞介素（IL）-12产生，以及产生干扰素-γ和IL-2的间质淋巴细胞的存在。相反，在高度易感小鼠中，TNF-α和IL-12的产生下调，这些小鼠还具有先天性抗真菌免疫缺陷以及肺淋巴细胞高水平产生IL-4和IL-10。在易感小鼠中，局部中和IL-4或IL-10或给予IL-12后，抗性增加。这些结果表明，与播散性曲霉病小鼠的观察结果相似，先天性免疫和Th1依赖性免疫在宿主抵抗IPA的防御中起重要作用。
