Rivera Johanna, Mukherjee Jean, Weiss Louis M, Casadevall Arturo
Department of Microbiology and Immunology and University of Massachusetts Medical School, Worcester, MA 01605, USA.
J Immunol. 2002 Apr 1;168(7):3419-27. doi: 10.4049/jimmunol.168.7.3419.
We investigated the pathogenesis of pulmonary Cryptococcus neoformans infection and passive Ab efficacy in mice deficient in inducible NO synthase (NOS2(-/-)) and the parental strain. Parental mice lived significantly longer than NOS2(-/-) mice after intratracheal infection, despite having a higher lung fungal burden. Administration of Ab reduced lung CFU in both NOS2(-/-) and parental mice, but prolonged survival and increased the inflammatory response only in parental mice. Ab administration was associated with increased serum nitrite and reduced polysaccharide levels in parental mice. Eosinophils were present in greater numbers in the lung of infected NOS2(-/-) mice than parental mice, irrespective of Ab administration. C. neoformans infection in NOS2(-/-) mice resulted in significantly higher levels of IFN-gamma, monocyte chemoattractant protein-1, and macrophage-inflammatory protein-1alpha than parental mice. Ab administration had different effects on infected NOS2(-/-) and parental mice with respect to IFN-gamma, monocoyte chemoattractant protein-1, and macrophage-inflammatory protein-1alpha levels. Ab administration increased lung levels of IFN-gamma in parental mice and reduced levels in NOS2(-/-) mice. The results indicate that NO is involved in the regulation of cytokine expression in response to cryptococcal pneumonia and is necessary for Ab efficacy against C. neoformans in mice. Our findings indicate a complex relationship between Ab efficacy against C. neoformans and cytokine expression, underscoring the interdependency of cellular and humoral defense mechanisms.
我们研究了肺新型隐球菌感染的发病机制以及诱导型一氧化氮合酶缺陷小鼠（NOS2(-/-)）和亲本品系小鼠中被动抗体的功效。气管内感染后，亲本小鼠的存活时间明显长于NOS2(-/-)小鼠，尽管其肺部真菌负荷更高。给予抗体可降低NOS2(-/-)小鼠和亲本小鼠的肺菌落形成单位（CFU），但仅能延长亲本小鼠的存活时间并增强炎症反应。给予抗体与亲本小鼠血清亚硝酸盐增加和多糖水平降低有关。无论是否给予抗体，感染的NOS2(-/-)小鼠肺中的嗜酸性粒细胞数量均多于亲本小鼠。与亲本小鼠相比，NOS2(-/-)小鼠感染新型隐球菌后，其γ干扰素、单核细胞趋化蛋白-1和巨噬细胞炎性蛋白-1α的水平显著更高。给予抗体对感染的NOS2(-/-)小鼠和亲本小鼠的γ干扰素、单核细胞趋化蛋白-1和巨噬细胞炎性蛋白-1α水平有不同影响。给予抗体可增加亲本小鼠肺中γ干扰素的水平，而降低NOS2(-/-)小鼠中的水平。结果表明，一氧化氮参与了对新型隐球菌肺炎的细胞因子表达调控，并且是小鼠中抗体抗新型隐球菌功效所必需的。我们的研究结果表明抗体抗新型隐球菌功效与细胞因子表达之间存在复杂关系，强调了细胞和体液防御机制的相互依赖性。
