Cell wall-associated alpha-glucan is instrumental for Mycobacterium tuberculosis to block CD1 molecule expression and disable the function of dendritic cell derived from infected monocyte |
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Authors: | Gagliardi Maria Cristina Lemassu Anne Teloni Raffaela Mariotti Sabrina Sargentini Valeria Pardini Manuela Daffé Mamadou Nisini Roberto |
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Institution: | Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena 299. 00161, Roma, Italy. |
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Abstract: | We previously described an escape mechanism exploited by Mycobacterium tuberculosis (Mtb) to prevent the generation of fully competent dendritic cells (DC). We have now tested the effect of isolated mycobacterial components on human monocyte differentiation into DC and demonstrated that cell wall (CW)-associated alpha-glucan induces monocytes to differentiate into DC (Glu-MoDC) with the same altered phenotype and functional behaviour of DC derived from Mtb-infected monocytes (Mt-MoDC). In fact, Glu-MoDC lack CD1 molecule expression, fail to upregulate CD80 and produce IL-10 but not IL-12. We also showed that Glu-MoDC are not able to prime effector T cells or present lipid antigens to CD1-restricted T-cell clones. Thus, we propose a mechanism of Mtb-monocyte interaction mediated by CW-associated alpha-glucan, which allows the bacterium to evade both innate and acquired immune responses. |
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