The CD16+/CD14+ monocyte subset gives rise to an altered dendritic cell population in tuberculosis

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

EUROPEAN JOURNAL OF IMMUNOLOGY

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2012 p. 1 - 7

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.