Hanekom Willem A, Mendillo Megan, Manca Claudia, Haslett Patrick A J, Siddiqui M Ruby, Barry Clifton, Kaplan Gilla
Department of Pediatrics, Division of Infectious Disease and Immunology, University of Miami School of Medicine, 1550 NW 10th Avenue, Suite 211 (D4-4), Miami, FL 33136, USA.
J Infect Dis. 2003 Jul 15;188(2):257-66. doi: 10.1086/376451. Epub 2003 Jul 9.
To induce effector immunity, dendritic cells (DCs) must differentiate into fully mature cells. We show that, after human monocyte-derived DCs were infected with virulent Mycobacterium tuberculosis, up-regulation of cellular-surface maturation markers was minimal and reversible. In the presence of a potent stimulus for maturation (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, and prostaglandin E2 [PGE2]), M. tuberculosis inhibited phenotypic DC maturation. M. tuberculosis-infected DCs had an impaired ability to induce allogeneic lymphoproliferation and activated autologous memory CD4+ and CD8+ T cells optimally only in the presence of TNF-alpha, IL-1beta, and PGE2. Thus, virulent M. tuberculosis inhibits phenotypic and functional maturation of human monocyte-derived DCs. This mechanism, which has been described elsewhere for various viruses and for the virulent mycobacterium M. leprae, may be a novel mechanism that this pathogen uses to evade the host's immune response.
为诱导效应免疫，树突状细胞（DCs）必须分化为完全成熟的细胞。我们发现，人类单核细胞衍生的DCs感染强毒力结核分枝杆菌后，细胞表面成熟标志物的上调程度极小且是可逆的。在存在强大的成熟刺激物（肿瘤坏死因子 [TNF]-α、白细胞介素 [IL]-1β 和前列腺素 E2 [PGE2]）的情况下，结核分枝杆菌抑制了DC的表型成熟。感染结核分枝杆菌的DC诱导同种异体淋巴细胞增殖的能力受损，并且仅在存在TNF-α、IL-1β 和 PGE2时才能最佳地激活自体记忆CD4+和CD8+ T细胞。因此，强毒力结核分枝杆菌抑制人类单核细胞衍生DC的表型和功能成熟。这种机制在其他地方已被描述用于各种病毒和强毒力麻风分枝杆菌，可能是该病原体用于逃避宿主免疫反应的一种新机制。
