Makino Masahiko, Maeda Yumi, Mukai Tetsu, Kaufmann Stefan H E
Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
Eur J Immunol. 2006 Jun;36(6):1443-52. doi: 10.1002/eji.200535727.
Dendritic cells (DC) are pivotal for initiation and regulation of innate and adaptive immune responses evoked by vaccination and natural infection. After infection, mycobacterial pathogens first encounter monocytes, which produce pro-inflammatory cytokines, including IL-1beta, TNF-alpha and IL-6. The role of these cytokines in DC maturation remains incompletely understood. Here, we show that maturation of DC from monocytes was impaired by pretreatment of monocytes with low doses of IL-1beta. Under these conditions, Mycobacterium leprae-infected DC failed to stimulate antigen-specific T cell responses. Expression of CD86 and CD83 and production of IL-12 in response to lipopolysaccharide and peptidoglycan were diminished. In contrast, these DC functions were not impaired by pretreatment with TNF-alpha, IL-6 or IL-10. When monocytes were infected with M. bovis Bacillus Calmette-Guérin, and subsequently differentiated to DC, the activity of these DC was suppressed as well. Thus, IL-1beta acts at early stages of differentiation of DC and impairs biological functions of DC at later stages. Therefore, production of IL-1beta by mycobacteria-infected antigen-presenting cells counteracts effective stimulation of innate and adaptive immune responses.
树突状细胞（DC）对于疫苗接种和自然感染引发的先天性和适应性免疫反应的启动和调节至关重要。感染后，分枝杆菌病原体首先遇到单核细胞，单核细胞产生促炎细胞因子，包括白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）。这些细胞因子在DC成熟中的作用仍未完全了解。在此，我们表明低剂量IL-1β预处理单核细胞会损害单核细胞来源的DC的成熟。在这些条件下，麻风分枝杆菌感染的DC无法刺激抗原特异性T细胞反应。对脂多糖和肽聚糖的反应中，CD86和CD83的表达以及IL-12的产生减少。相反，TNF-α、IL-6或IL-10预处理不会损害这些DC功能。当单核细胞感染卡介苗，随后分化为DC时，这些DC的活性也受到抑制。因此，IL-1β在DC分化的早期起作用，并在后期损害DC的生物学功能。因此，分枝杆菌感染的抗原呈递细胞产生的IL-1β会抵消对先天性和适应性免疫反应的有效刺激。
