The CD16+ Monocyte subset gives rise to an altered dendritic cell population in tuberculosis.

BALBOA, LUCIANA; ; ROMERO, MARÍA; ; BRANDA, ADRIANA; ; ZAMBRANA, NELLY;; MUSELLA, ROSA; ; CASTAGNINO, JORGE; ; ABBATE, EDUARDO; ; SASIAIN, MARÍA; ; ALEMÁN, MERCEDES.

Congreso; Primer Congreso Franco-Argentino de Inmunología; 2010

During a chronic infection such as tuberculosis (TB), the pool of tissue dendritic cells (DC) must be renewed by recruitment of both circulating DC progenitors and monocytes (Mo). Mo can be classified into at least two subpopulations with distinct phenotypical and functional characteristics: classical CD16– and nonclassical CD16+. We have demonstrated that Mo from TB patients showed an enrichment of the circulating CD16+ subset and presented an altered differentiation process characterized by the generation of CD1alow/CD14+/DC-SIGNlow/CD86high cells which induced low specific T cell proliferation in response to Mycobacterium tuberculosis. Therefore, we wondered if this enlarged CD16+ Mo subset could be responsible for the altered Mo differentiation into DC in TB patients.Mo or isolated Mo subsets were differentiated in vitro in presence of IL-4 and GM-CSF for 6 days. Afterwards, CD1a, CD14, CD86 and DC-SIGN expression was evaluated by flow cytometry.We found a positive correlation between the percentages of CD16+ Mo and of DC-SIGNlow/CD86high altered DC population (p<0.05, n=18). We analyzed the acquisition of DC phenotype and observed that CD16+ precursors did express neither CD1a nor DC-SIGN and showed high expression of CD86 at 20h from the onset of the differentiation (p<0.05). Besides, the differentiation into DC from the isolated CD16+ subset gave rise to a main population CD1alow/DC-SIGNlow, while the CD16- subset gave rise to a main population CD1a+/DC-SIGNhigh (p<0.05). In line with this, the addition of CD16+ cells in CD16depleted-Mo from healthy subjects generated CD1alow/DC-SIGNlow cells (p<0.05). Finally, the depletion of CD16+Mo improved DC differentiation in TB patients. These results demonstrate that the CD16+ Mo subset fails to give rise to CD1a+/DC-SIGNhigh cells. Therefore, we were able to link the impairment of DC generation with the expansion of the CD16+ Mo in TB patients.