DIVERGING BIOLOGICAL ROLES AMONG HUMAN MONOCYTE SUBSETS IN THE CONTEXT OF TB INFECTION

BALBOA L; BARRIOS-PAYAN J; GONZÁLEZ-DOMÍNGUEZ E; LASTRUCCI C; LUGO-VILLARINO G; MATA-ESPINOZA D; SCHIERLOH P

Mar del Plata

Congreso; LXII Reunión Anual de la Sociedad Argentina de Inmunología; 2014

Sociedad Argentina de Inmunología (SAI)

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the most devastating human diseases. In chronic infections such as TB, circulating monocytes (Mo) arrive to the infected site and give rise to macrophages and dendritic cells (DC). We demonstrated that human CD16pos Mo expand in TB patients, correlate with disease severity and are refractory to DC differentiation, suggesting diverging biological roles among Mo subsets. So, we investigated if human Mo subsets (CD16neg and CD16pos) are differentially recruited to lungs, and whether this event could affect the outcome of the infection in a humanized mice model. We found that CD16neg Mo were more prone to migrate in response to Mtb-derived gradients, while CD16pos Mo moved under steady state conditions, across naked inserts (P 0.05, n=8) and 3D-scaffolds such as Matrigel (P 0.05, n=5). To confirm these migration patterns, we transferred CD16neg or CD16pos Mo orotracheally into Mtb-infected SCID/Beige mice and compared their abilities to traffic from the alveolar spaces to the lungs. Unlike CD16pos Mo, the % of human cells (HLA-DRpos) recovered from lungs of CD16neg Mo-transferred mice were increased under infectious conditions (P 0.05, n=5). In terms of the host immune response, the adoptive transfer of the CD16neg subset was characterized by the lung infiltration of cells producing TNF-α, IL-1-β, IL-10, TGF- β assessed by IHC (P 0.05, n=8, 15 random fields/lung). Moreover, the transfer of CD16neg Mo decreased the bacterial charge in the lungs (P 0.05, n=7). When challenged in vitro with Mtb, CD16neg Mo were indeed more resistant to bacillus intracellular growth (P 0.05, n=4) and induced higher levels of respiratory burst than the other subset (P 0.05, n=7). Collectively, our results constitute clear evidence in favor of a differential contribution of human Mo subsets throughout the course of the infection, shedding light on a key aspect of the physiopathology of TB.