Vaughan Andrew T, Gorringe Andrew, Davenport Victoria, Williams Neil A, Heyderman Robert S
Department of Cellular and Molecular Medicine, School of Medical Science, University of Bristol, Bristol, United Kingdom.
J Immunol. 2009 Feb 15;182(4):2231-40. doi: 10.4049/jimmunol.0802531.
The normal flora that colonizes the mucosal epithelia has evolved diverse strategies to evade, modulate, or suppress the immune system and avoid clearance. Neisseria lactamica and Neisseria meningitidis are closely related obligate inhabitants of the human upper respiratory tract. N. lactamica is a commensal but N. meningitidis is an opportunistic pathogen that occasionally causes invasive disease such as meningitis and septicemia. We demonstrate that unlike N. meningitidis, N. lactamica does not prime the development of mucosal T or B cell memory during the peak period of colonization. This cannot be explained by the induction of peripheral tolerance or regulatory CD4(+)CD25(+) T cell activity. Instead, N. lactamica mediates a B cell-dependent mitogenic proliferative response that is absent to N. meningitidis. This mitogenic response is associated with the production of T cell-independent polyclonal IgM that we propose functions by shielding colonizing N. lactamica from the adaptive immune system, maintaining immunological ignorance in the host. We conclude that, in contrast to N. meningitidis, N. lactamica maintains a commensal relationship with the host in the absence of an adaptive immune response. This may prolong the period of susceptibility to colonization by both pathogenic and nonpathogenic Neisseria species.
定殖于黏膜上皮的正常菌群已进化出多种策略来逃避、调节或抑制免疫系统并避免被清除。乳酸奈瑟菌和脑膜炎奈瑟菌是人类上呼吸道密切相关的专性定殖菌。乳酸奈瑟菌是共生菌,而脑膜炎奈瑟菌是机会致病菌,偶尔会引发侵袭性疾病,如脑膜炎和败血症。我们证明,与脑膜炎奈瑟菌不同,乳酸奈瑟菌在定殖高峰期不会引发黏膜T或B细胞记忆的发育。这无法通过外周耐受的诱导或调节性CD4(+)CD25(+) T细胞活性来解释。相反,乳酸奈瑟菌介导了一种B细胞依赖性的促有丝分裂增殖反应,而脑膜炎奈瑟菌则没有这种反应。这种促有丝分裂反应与非T细胞依赖性多克隆IgM的产生有关,我们认为其作用是保护定殖的乳酸奈瑟菌免受适应性免疫系统的影响,在宿主体内维持免疫忽视状态。我们得出结论,与脑膜炎奈瑟菌不同,乳酸奈瑟菌在缺乏适应性免疫反应的情况下与宿主维持共生关系。这可能会延长宿主对致病性和非致病性奈瑟菌属定殖易感的时期。