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

ABSTRACT: 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?) and its impact in the subsequent immune response. In response to various signals M? may undergo classical-M1 (M1-M?) or alternative-M2 (M2-M?) activation. Until now there are no reports of the gonococcus effects on human M? polarization. We assessed the phagocytic ability of monocyte-derived M? (MDM) upon gonococcal infection by immunofluorescence and gentamicin protection experiments. Then, we evaluated cytokine profile and M1/M2 specific-surface markers on M? challenged with N. gonorrhoeae and their proliferative effect on T cells. Our findings lead us to suggest N. gonorrhoeae stimulates a M2-M? phenotype in which some of the M2b and none of the M1-M?-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? 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? 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.

SUBMITTER: Ortiz MC 

PROVIDER: S-EPMC4488386 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature