Neisseria gonorrhoeae Modulates Immunity by Polarizing Human Macrophages to a M2 Profile

Artículo de publicación ISI ; Current data suggest that Neisseria gonorrhoeae is able to suppress the protective immune response at different levels, such as B and T lymphocytes and antigen-presenting cells. The present report is focused on gonococcus evasion mechanism on macrophages (M phi) and its impact in the subsequent immune response. In response to various signals M phi may undergo classical-M1 (M1-M phi) or alternative-M2 (M2-M phi) activation. Until now there are no reports of the gonococcus effects on human M phi polarization. We assessed the phagocytic ability of monocyte-derived M phi (MDM) upon gonococcal infection by immunofluorescence and gentamicin protection experiments. Then, we evaluated cytokine profile and M1/M2 specific-surface markers on M phi challenged with N. gonorrhoeae and their proliferative effect on T cells. Our findings lead us to suggest N. gonorrhoeae stimulates a M2-M phi phenotype in which some of the M2b and none of the M1-M phi-associated markers are induced. Interestingly, N. gonorrhoeae exposure leads to upregulation of a Programmed Death Ligand 1 (PD-L1), widely known as an immunosuppressive molecule. Moreover, functional results showed that N. gonorrhoeae-treated M phi are unable to induce proliferation of human T-cells, suggesting a more likely regulatory phenotype. Taken together, our data show that N. gonorroheae interferes with M phi polarization. This study has important implications for understanding the mechanisms of clearance versus long-term persistence of N. gonorroheae infection and might be applicable for the development of new therapeutic strategies. ; Fondo Nacional de Ciencia y Tecnologia FONDECYT 11110304