Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK

LUCIANA BALBOA; MARÍA M ROMERO; EVANGELINA LABORDE; CARMEN A SABIO Y GARCÍA; JUAN I BASILE; PABLO SCHIERLOH; NOEMÍ YOKOBORI; ROSA M MUSELLA; JORGE CASTAGNINO; SILVIA DE LA BARRERA; MARÍA C SASIAIN; MERCEDES ALEMÁN

EUROPEAN JOURNAL OF IMMUNOLOGY

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2013 vol. 43 p. 335 - 347

0014-2980

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. Thus, the phenotype and ability to stimulate Mtb-specific memory clones from Mo subsets-DCs were assessed. We found that CD16- Mos differentiated into CD1a+DC-SIGNhigh cells achieving an efficient recall response, while CD16+ Mos differentiated into a CD1a-DC-SIGNlow population characterized by a poor mycobacterial Ag-presenting capacity. The high and sustained p-p38 expression observed in CD16+ Mos was involved in the altered DC profile given that its blockage restored DCs phenotype and its activation impaired CD16- Mos differentiation. Furthermore, the depletion of CD16+ Mos indeed improved the differentiation of Mos from TB patients towards CD1a+DC-SIGNhigh 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.