Gomes M S, Flórido M, Pais T F, Appelberg R
Laboratory of Microbiology and Immunology of Infection, Institute for Molecular and Cell Biology, University of Porto, Portugal.
J Immunol. 1999 Jun 1;162(11):6734-9.
Mice genetically deficient in the inducible NO synthase gene (iNOS-/-) were used to study the role played by NO during infection by Mycobacterium avium. iNOS-/- macrophages were equally able to restrict M. avium growth in vitro following stimulation by IFN-gamma and TNF-alpha as macrophages from wild-type mice. In vivo, the infection progressed at similar rates in wild-type and NO-deficient mice during the first 2 mo of infection, but the latter mice were subsequently more efficient in clearing the mycobacteria than the former. The increased resistance of iNOS-/- mice was associated with higher IFN-gamma levels in the serum and following in vitro restimulation of spleen cells with specific Ag, increased formation of granulomas and increased survival of CD4+ T cells. We show that NO is not involved in the antimycobacterial mechanisms of M. avium-infected macrophages and, furthermore, that it exacerbates the infection by causing the suppression of the immune response to the pathogen.
利用基因敲除诱导型一氧化氮合酶基因（iNOS-/-）的小鼠来研究一氧化氮在鸟分枝杆菌感染过程中所起的作用。iNOS-/-巨噬细胞在受到γ干扰素和肿瘤坏死因子-α刺激后，在体外限制鸟分枝杆菌生长的能力与野生型小鼠的巨噬细胞相当。在体内，感染的前两个月，野生型和一氧化氮缺陷型小鼠的感染进展速度相似，但随后后者清除分枝杆菌的效率比前者更高。iNOS-/-小鼠抵抗力增强与血清中γ干扰素水平升高有关，在用特异性抗原体外再次刺激脾细胞后，肉芽肿形成增加，CD4+T细胞存活率提高。我们发现，一氧化氮不参与鸟分枝杆菌感染的巨噬细胞的抗分枝杆菌机制，此外，它通过抑制对病原体的免疫反应而加剧感染。
