title: 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 (MФ) and its impact in the subsequent immune response. In response to various signals MФ may undergo classical-M1 (M1-MФ) or alternative-M2 (M2-MФ) activation. Until now there are no reports of the gonococcus effects on human MФ polarization. We assessed the phagocytic ability of monocyte-derived MФ (MDM) upon gonococcal infection by immunofluorescence and gentamicin protection experiments. Then, we evaluated cytokine profile and M1/M2 specific-surface markers on MФ challenged with N. gonorrhoeae and their proliferative effect on T cells. Our findings lead us to suggest N. gonorrhoeae stimulates a M2-MФ phenotype in which some of the M2b and none of the M1-MФ-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 MФ 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 MФ 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.
authors.affiliation: Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología. Universidad de Chile, Santiago, Chile.
authors.forename: María Carolina
authors.initials: MC
authors.lastname: Ortiz
authors.affiliation: Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología. Universidad de Chile, Santiago, Chile.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lefimil
authors.affiliation: Center for Integrative Medicine and Innovative Science, Facultad de Medicina. Universidad Andrés Bello, Santiago, Chile.
authors.forename: Paula I
authors.initials: PI
authors.lastname: Rodas
authors.affiliation: Departamento de Odontología Conservadora, Facultad de Odontología. Universidad de Chile, Santiago, Chile.
authors.forename: Rolando
authors.initials: R
authors.lastname: Vernal
authors.affiliation: Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina. Universidad de Chile, Santiago, Chile.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Lopez
authors.affiliation: Laboratorio de Inmunología, Departamento de Biología, Facultad de Química y Biología. Universidad de Santiago de Chile, Santiago, Chile.
authors.forename: Claudio
authors.initials: C
authors.lastname: Acuña-Castillo
authors.affiliation: Laboratorio de Inmunología, Departamento de Biología, Facultad de Química y Biología. Universidad de Santiago de Chile, Santiago, Chile.
authors.forename: Mónica
authors.initials: M
authors.lastname: Imarai
authors.affiliation: Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología. Universidad de Chile, Santiago, Chile.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Escobar
mesh_terms: D060890:B7-H1 Antigen / Q000276:immunology; D049109:Cell Proliferation / Q000502:physiology; D006069:Gonorrhea / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human