Guangdong Key Laboratory for Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen 518020, China; Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen 518020, China.
Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou 510120, China.
Tuberculosis (Edinb). 2014 May;94(3):238-44. doi: 10.1016/j.tube.2013.12.003. Epub 2013 Dec 20.
IL-22 has been suggested to play an important role in immune response against Mycobacterium tuberculosis infection. However, the exact role of IL-22 in human tuberculosis (TB) infection remains unclear and the regulatory mechanism of IL-22 response in human TB is unknown. In this study, we observed that successful anti-tuberculosis treatment induced an enhanced and sustained M. tuberculosis antigen-specific IL-22 response, correlated with the decrease of the frequencies of CD19(+)CD5(+)CD1d(+) regulatory B cells. We also found that depletion of CD19(+) B cells significantly enhanced M. tuberculosis antigen-specific IL-22 production by peripheral blood mononuclear cells. More importantly, we observed that purified CD19(+) B cells, and more efficiently, CD19(+)CD5(+)CD1d(+) regulatory B cells, suppressed IL-22 production. In summary, we showed here for the first time that effective anti-tuberculosis treatment restores M. tuberculosis antigen-specific IL-22 response through a novel mechanism by reducing the frequencies of CD19(+)CD5(+)CD1d(+) regulatory B cells in human TB.
IL-22 被认为在针对结核分枝杆菌感染的免疫反应中发挥重要作用。然而，IL-22 在人类结核病（TB）感染中的确切作用仍不清楚，人类 TB 中 IL-22 反应的调节机制也未知。在本研究中，我们观察到成功的抗结核治疗诱导了增强和持续的结核分枝杆菌抗原特异性 IL-22 反应，与 CD19(+)CD5(+)CD1d(+)调节性 B 细胞频率的降低相关。我们还发现，耗尽 CD19(+) B 细胞可显著增强外周血单核细胞对结核分枝杆菌抗原特异性 IL-22 的产生。更重要的是，我们观察到纯化的 CD19(+) B 细胞，更有效地是 CD19(+)CD5(+)CD1d(+)调节性 B 细胞，可抑制 IL-22 的产生。总之，我们首次表明，有效的抗结核治疗通过降低人类 TB 中 CD19(+)CD5(+)CD1d(+)调节性 B 细胞的频率，通过一种新的机制恢复结核分枝杆菌抗原特异性 IL-22 反应。
