Down-regulation of the afferent phase of T cell-mediated pulmonary inflammation and immunity by a high melanin-producing strain of Cryptococcus neoformans.
Down-regulation of the afferent phase of T cell-mediated pulmonary inflammation and immunity by a high melanin-producing strain of Cryptococcus neoformans.
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DOI：
10.4049/jimmunol.155.7.3507
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发表时间：
1995-10
影响因子：
4.4
通讯作者：
G. Huffnagle;Gwo-hsiao Chen;Jeffrey L. Curtis;R. McDonald;Robert M. Strieter;G. Toews
中科院分区：
文献类型：
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作者：
G. Huffnagle;Gwo-hsiao Chen;Jeffrey L. Curtis;R. McDonald;Robert M. Strieter;G. Toews
隐球菌毒力因子与参与产生保护性细胞介导免疫的白细胞之间的相互作用尚未明确。气管内接种新型隐球菌菌株 52 诱导了强烈的 T 细胞介导的肺部炎症反应，从而控制了生物体的生长。相比之下，145菌株诱导的肺部炎症反应延迟发作，发展缓慢，并且无法有效控制感染。此外，145株感染小鼠肺淋巴结中隐球菌特异性淋巴细胞的扩增和血清中特异性抗体的滴度均显着减少。在已知的隐球菌毒力因子中，这两种菌株仅在黑色素产生方面存在差异（52-低和145-高）。黑色素阴性的热灭活菌株 145 隐球菌 (HKC-145) 在体外诱导肺泡巨噬细胞产生 TNF-α，并刺激隐球菌特异性淋巴细胞增殖。相比之下，高黑色素含量的 HKC-145 抑制 TNF-α 的产生和淋巴增殖。在体内，感染黑色素低菌株 52（而非黑色素高菌株 145）的小鼠支气管肺泡灌洗液中的 TNF-α 水平升高。同时感染 145 株和 52 株的小鼠会产生肺部炎症反应，从而提高长期存活率。总而言之，这些研究表明，黑色素并不能保护隐球菌不被体内招募的、激活的效应细胞消除。但黑色素可以抑制宿主防御对生物体的识别，从而下调 T 细胞介导的免疫的传入阶段，例如 TNF-α 的产生和淋巴细胞增殖。
The interaction(s) between cryptococcal virulence factors and leukocytes involved in generating protective cell-mediated immunity is not well defined. Intratracheal inoculation of Cryptococcus neoformans strain 52 induced a vigorous T cell-mediated pulmonary inflammatory response that controlled the growth of the organism. In contrast, strain 145 induced a pulmonary inflammatory response that was delayed in onset, slower to develop, and ineffective in controlling the infection. In addition, the expansion of cryptococcus-specific lymphocytes in the pulmonary lymph nodes and titer of specific Abs in the serum of strain 145-infected mice were both diminished markedly. Of the known cryptococcal virulence factors, these two strains differed only in melanin production (52-low and 145-high). Heat-killed strain 145 cryptococci (HKC-145) that had been rendered melanin-negative induced TNF-alpha production by alveolar macrophages in vitro and stimulated vigorous cryptococcus-specific lymphoproliferation. In contrast, high melanin-containing HKC-145 inhibited TNF-alpha production and lymphoproliferation. In vivo, mice infected with melanin low strain 52, but not melanin high strain 145, had elevated levels of TNF-alpha in the bronchoalveolar lavage fluid. Mice co-infected with strains 145 and 52 generated a pulmonary inflammatory response resulting in increased long-term survival. Taken together, these studies demonstrate that melanin does not protect cryptococci from being eliminated in vivo by recruited, activated effector cells; but melanin can inhibit the recognition of the organism by host defenses, thereby down-regulating the afferent phase of T cell-mediated immunity, e.g., TNF-alpha production and lymphoproliferation.