Impaired CD16+ monocytes differentiation into dendritic cells is mediated by p38-mapk in tuberculosis

BALBOA LUCIANA; ROMERO MERCEDES; LABORDE, EVANGELINA;; MUSELLA ROSA; SASIAIN MARÍA DEL CARMEN; ALEMÁN MERCEDES

Lima

Congreso; Inmuno Perú 2012; 2012

Asociación latinoamericana de Inmunología

Background: Tuberculosis (TB) remains as one of the world's most pernicious diseases mainly due to immune evasion strategies displayed by Mycobacterium tuberculosis (Mtb). Blood monocytes (Mo) represent an important source of dendritic cells (DC) during chronic infections; consequently the alteration of their differentiation constitutes an escape mechanism leading to mycobacterial persistence. We evaluated if the increased CD16+/CD16- Mo ratio displayed by TB patients could explain their impaired differentiation into DC. Methods: Magnetically isolated Mo subsets were differentiated into DC with IL-4 and GM-CSF, and their phenotype and ability to stimulate Mtb-specific T-cells were assessed. Results: CD16- Mo differentiated into efficient antigen presenting CD1a+DC-SIGNhigh DC while CD16+ Mo differentiated into poor antigen presenting CD1alowDC-SIGNlow DC. The addition of CD16+ Mo to CD16- Mo prompted an altered DC profile and CD16+-depleted Mo from TB patients gave rise to CD1a+DC-SIGNhigh. Interestingly, CD16+ Mo did not impair the CD16- Mo differentiation. Finally, the differential p38 MAPK activity in Mo subsets modulated their capacity to generate DC. Conclusions: Mo from TB patients are less prone to differentiate in vitro into DC due to their increased proportion of CD16+ Mo suggesting that during Mtb infection, Mo subsets may have different fates after entering lungs.