Taramelli D, Malabarba M G, Sala G, Basilico N, Cocuzza G
Institute of Medical Microbiology, School of Medicine, University of Milan, Italy.
J Med Vet Mycol. 1996 Jan-Feb;34(1):49-56.
Aspergillus fumigatus is an opportunistic pathogen responsible for severe, invasive infections in neutropenic hosts. Lung clearance of A. fumigatus conidia seems to be mediated by phagocytic cells and oxygen radicals. It is not known if cytokines or nitrogen radicals are also involved. We tested for the production of TNF alpha, IL-1 and nitric oxide (NO) after stimulation of mouse macrophages with the fungus. We found that both cytokines, but not NO, were produced in a dose-dependent manner during the first 24 h of culture. Except for a faster kinetic, no appreciable differences were seen between alveolar and peritoneal macrophages. Furthermore, both hyphae and conidia, either alive or killed, were capable of inducing cytokines production. However, among different Aspergillus spp. only A. fumigatus and A. flavus seemed to induce significant amount of TNF alpha and IL-1, whereas A. terreus and A. niger were less effective. In no case could we detect production of NO. Finally, macrophages from dexamethasone-treated mice failed to produce cytokines in response to A. fumigatus conidia. These results indicate that in normal hosts inflammatory cytokines contribute to the natural response against Aspergillus infections and suggest that the impairment of cytokine production, in immunodepressed patients, may favour the growth and spread of the fungus.
烟曲霉是一种机会致病菌，可导致中性粒细胞减少宿主发生严重的侵袭性感染。烟曲霉分生孢子的肺清除似乎是由吞噬细胞和氧自由基介导的。目前尚不清楚细胞因子或氮自由基是否也参与其中。我们在用该真菌刺激小鼠巨噬细胞后检测了肿瘤坏死因子α（TNFα）、白细胞介素-1（IL-1）和一氧化氮（NO）的产生。我们发现，在培养的最初24小时内，这两种细胞因子均呈剂量依赖性产生，而NO则未产生。除了动力学更快外，肺泡巨噬细胞和腹腔巨噬细胞之间未见明显差异。此外，活的或死的菌丝和分生孢子均能够诱导细胞因子的产生。然而，在不同的曲霉属物种中，只有烟曲霉和黄曲霉似乎能诱导产生大量的TNFα和IL-1，而土曲霉和黑曲霉的效果较差。在任何情况下我们都未检测到NO的产生。最后，来自地塞米松处理小鼠的巨噬细胞对烟曲霉分生孢子无反应，未能产生细胞因子。这些结果表明，在正常宿主中，炎性细胞因子有助于对曲霉感染的天然反应，并提示在免疫抑制患者中细胞因子产生的受损可能有利于真菌的生长和扩散。
