IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAP kinase.
Autor/es:
BALBOA L; ROMERO MM; LABORDE E; SABIO Y GARCÍA CA; BASILE JI; SCHIERLOH P; YOKOBORI N; MUSELLA RM
Revista:
EUROPEAN JOURNAL OF IMMUNOLOGY
Editorial:
WILEY-V C H VERLAG GMBH
Referencias:
Lugar: Weinheim; Año: 2013 vol. 43 p. 335 - 347
ISSN:
0014-2980
Resumen:
Tuberculosis (TB) is one of the world´s most pernicious diseases mainly due to immune evasion strategies displayed by its causative agent Mycobacterium tuberculosis (Mtb). Blood monocytes (Mos) represent an important source of DCs during chronic infections; consequently, the alteration of their differentiation constitutes an escape mechanism leading to mycobacterial persistence. We evaluated whether the CD16(+) /CD16(-) Mo ratio could be associated with the impaired Mo differentiation into DCs found in TB patients. The phenotype and ability to stimulate Mtb-specific memory clones DCs from isolated Mo subsets were assessed. We found that CD16(-) Mos differentiated into CD1a(+) DC-SIGN(high) cells achieving an efficient recall response, while CD16(+) Mos differentiated into a CD1a(-) DC-SIGN(low) population characterized by a poor mycobacterial Ag-presenting capacity. The high and sustained phosphorylated p38 expression observed in CD16(+) Mos was involved in the altered DC profile given that its blockage restored DC phenotype and its activation impaired CD16(-) Mo differentiation. Furthermore, depletion of CD16(+) Mos indeed improved the differentiation of Mos from TB patients towards CD1a(+) DC-SIGN(high) DCs. Therefore, Mos from TB patients are less prone to differentiate into DCs due to their increased proportion of CD16(+) Mos, suggesting that during Mtb infection Mo subsets may have different fates after entering the lungs.