CONICET | Buscador de Institutos y Recursos Humanos

After bacterial products recognition macrophages initiate an immune response for removal of the microbes. Proper polarization of macrophages is critical for bacterial clearance. During microbial infection, macrophages are polarized to classically or alternatively activated cells (M1 or M2, respectively) in response to microbial components and host immune mediators. Recently we have demonstrated that B. pertussis (Bp) has the ability to manipulate the host defense response eventually enabling its own survival and replication inside the macrophages. In the present study we examined the evolution of macrophage phenotype during the Bp intracellular survival and proliferation. To this end, primary peripheral blood mononuclear cells (PBMC) were differentiated into macrophages in the presence of GM-CSF; GM-CSF + INF-gamma/LPS; M-CSF + IL-4 or M-CSF + IL10 to obtain the phenotypes M0, M1, M2a or M2c, respectively. Intracellular Bp infection evolution was determined by FISH staining and confocal microscopy. Macrophage expression of CD40, CD80, CD206, CD209 and CD163 was determined at 3 and 48 hours after infection. Three hours post infection macrophages cultured under all conditions displayed an increase in CD40 and CD80 expression and a decrease in CD206, CD209 and CD163 expressions as compared with the uninfected control. Forty eight hours post infection cells in which Bp infection had developed showed a decrease in CD40 and CD80 expression and an increase of CD209 and CD163 in all macrophage phenotypes (M0, M1, M2a and M2c) as compared with the uninfected population of the respective phenotype. These results indicate that early after bacterial phagocytosis macrophages develop an M1 like phenotype. However, as the intracellular infection progresses infected cells of any macrophage phenotype turned into an M2 like type, indicating the extraordinary ability of this pathogen to induce a permissive environment for its survival within human macrophages.