Segal Leopoldo N, Clemente Jose C, Li Yonghua, Ruan Chunhai, Cao Jane, Danckers Mauricio, Morris Alison, Tapyrik Sarah, Wu Benjamin G, Diaz Philip, Calligaro Gregory, Dawson Rodney, van Zyl-Smit Richard N, Dheda Keertan, Rom William N, Weiden Michael D
Division of Pulmonary, Critical Care and Sleep Medicine, School of Medicine, New York University, New York, NY 10016, USA.
Icahn Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Cell Host Microbe. 2017 Apr 12;21(4):530-537.e4. doi: 10.1016/j.chom.2017.03.003. Epub 2017 Mar 30.
Despite the immune-reconstitution with antiretroviral therapy (ART), HIV-infected individuals remain highly susceptible to tuberculosis (TB) and have an enrichment of oral anaerobes in the lung. Products of bacterial anaerobic metabolism, like butyrate and other short-chain fatty acids (SCFAs), induce regulatory T cells (Tregs). We tested whether SCFAs contribute to poor TB control in a longitudinal cohort of ART-treated HIV-infected South Africans. Increase in serum SCFAs was associated with increased TB susceptibility. SCFAs inhibited IFN-γ and IL-17A production in peripheral blood mononuclear cells from HIV-infected ART-treated individuals in response to M. tuberculosis antigen stimulation. Pulmonary SCFAs correlated with increased oral anaerobes, such as Prevotella in the lung, and with M. tuberculosis antigen-induced Tregs. Metabolites from anaerobic bacterial fermentation may, therefore, increase TB susceptibility by suppressing IFN-γ and IL-17A production during the cellular immune response to M. tuberculosis.
尽管抗逆转录病毒疗法（ART）可实现免疫重建，但HIV感染者仍极易感染结核病（TB），且肺部存在口腔厌氧菌富集现象。细菌厌氧代谢产物，如丁酸盐和其他短链脂肪酸（SCFAs），可诱导调节性T细胞（Tregs）。我们在接受ART治疗的南非HIV感染者纵向队列中测试了SCFAs是否会导致结核病控制不佳。血清SCFAs升高与结核病易感性增加相关。SCFAs抑制了接受ART治疗的HIV感染者外周血单核细胞在结核分枝杆菌抗原刺激下产生IFN-γ和IL-17A。肺部SCFAs与肺部口腔厌氧菌（如普雷沃菌属）增加以及结核分枝杆菌抗原诱导的Tregs相关。因此，厌氧细菌发酵产生的代谢产物可能通过在细胞免疫反应中抑制对结核分枝杆菌产生IFN-γ和IL-17A，从而增加结核病易感性。
