Martino Angelo, Sacchi Alessandra, Volpe Elisabetta, Agrati Chiara, De Santis Rafaella, Pucillo Leopoldo Paolo, Colizzi Vittorio, Vendetti Silvia
National Institute for Infectious Diseases Lazzaro Spallanzani, Rome, Italy.
J Clin Immunol. 2005 Jul;25(4):365-75. doi: 10.1007/s10875-005-4188-x.
Mycobacterium smegmatis infects human monocytes that can be precursors of dendritic cells. We tested whether the interaction of M. smegmatis with monocytes modulated their differentiation into dendritic cells. We found that M. smegmatis-infected monocytes differentiated into CD1a-CCR7+ dendritic cells in the presence of GM-CSF and IL-4 and acquired a mature phenotype since they expressed CD83 molecules in the absence of maturation stimuli. Dendritic cells derived from M. smegmatis-infected monocytes stimulated with bacterial products, produced IL-10 and still retained the capacity to produce IL-12. Consequently, they polarized naïve T lymphocytes towards a mixed Th1/Th2 immune response inducing both IFN-gamma and IL-4 production. These findings suggest that the exposure to environmental mycobacteria could modulate the differentiation of dendritic cells making them able to migrate into secondary lymphoid organs and modulate the adaptive immune response. This could explain one of the mechanisms by which environmental mycobacteria can influence the immune response to pathogenic species.
耻垢分枝杆菌可感染人类单核细胞，而单核细胞可能是树突状细胞的前体。我们测试了耻垢分枝杆菌与单核细胞的相互作用是否会调节其向树突状细胞的分化。我们发现，在存在粒细胞巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-4（IL-4）的情况下，被耻垢分枝杆菌感染的单核细胞可分化为CD1a-CCR7 +树突状细胞，并获得成熟表型，因为它们在没有成熟刺激的情况下表达CD83分子。来自被耻垢分枝杆菌感染的单核细胞的树突状细胞在用细菌产物刺激后，会产生白细胞介素-10（IL-10），并且仍保留产生白细胞介素-12（IL-12）的能力。因此，它们使幼稚T淋巴细胞偏向混合的Th1/Th2免疫反应，诱导干扰素-γ（IFN-γ）和白细胞介素-4的产生。这些发现表明，接触环境分枝杆菌可能会调节树突状细胞的分化，使其能够迁移至次级淋巴器官并调节适应性免疫反应。这可以解释环境分枝杆菌影响对致病菌种免疫反应的其中一种机制。
