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

Ortiz MC, Lefimil C, Rodas PI, Vernal R, Lopez M, Acuña-Castillo C, Imarai M, Escobar A - PLoS ONE (2015)

Bottom Line: Until now there are no reports of the gonococcus effects on human MФ polarization.Moreover, functional results showed that N. gonorrhoeae-treated MФ are unable to induce proliferation of human T-cells, suggesting a more likely regulatory phenotype.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.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología. Universidad de Chile, Santiago, Chile.

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.

No MeSH data available.


Related in: MedlinePlus

N. gonorrhoeae induced M1 and M2-MΦ associated markers.Expression of M1 and M2-MΦ distinctive surface markers were evaluated in GC-treated MΦ by flow cytometry (monocytic cells gated). (A) Representative histograms for each evaluated marker from at least three independent experiments. (B) Mean fluorescence intensity (MFI) average for each marker. Data represent at least 3 independent experiments; bars indicate SEM; * p < 0.05. ** p < 0.01. *** p < 0.001 indicates significant induction compared to non-stimulated MΦ (M0-MΦ).
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pone.0130713.g002: N. gonorrhoeae induced M1 and M2-MΦ associated markers.Expression of M1 and M2-MΦ distinctive surface markers were evaluated in GC-treated MΦ by flow cytometry (monocytic cells gated). (A) Representative histograms for each evaluated marker from at least three independent experiments. (B) Mean fluorescence intensity (MFI) average for each marker. Data represent at least 3 independent experiments; bars indicate SEM; * p < 0.05. ** p < 0.01. *** p < 0.001 indicates significant induction compared to non-stimulated MΦ (M0-MΦ).

Mentions: Once the M0-MΦ capacity to interact and internalize N. gonorrhoeae is confirmedwe evaluated several M1 and M2-MФ-associated markers by flow cytometry 24 hours post N. gonorrhoeae exposure. Stimulation with N. gonorrhoeae increased the expression of the M2-MФ-associated marker CD163 at all the MOIs tested. CD206 M2-MФ-associated marker, in contrast, was only increased at MOI 1000 (Fig 2).


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

Ortiz MC, Lefimil C, Rodas PI, Vernal R, Lopez M, Acuña-Castillo C, Imarai M, Escobar A - PLoS ONE (2015)

N. gonorrhoeae induced M1 and M2-MΦ associated markers.Expression of M1 and M2-MΦ distinctive surface markers were evaluated in GC-treated MΦ by flow cytometry (monocytic cells gated). (A) Representative histograms for each evaluated marker from at least three independent experiments. (B) Mean fluorescence intensity (MFI) average for each marker. Data represent at least 3 independent experiments; bars indicate SEM; * p < 0.05. ** p < 0.01. *** p < 0.001 indicates significant induction compared to non-stimulated MΦ (M0-MΦ).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488386&req=5

pone.0130713.g002: N. gonorrhoeae induced M1 and M2-MΦ associated markers.Expression of M1 and M2-MΦ distinctive surface markers were evaluated in GC-treated MΦ by flow cytometry (monocytic cells gated). (A) Representative histograms for each evaluated marker from at least three independent experiments. (B) Mean fluorescence intensity (MFI) average for each marker. Data represent at least 3 independent experiments; bars indicate SEM; * p < 0.05. ** p < 0.01. *** p < 0.001 indicates significant induction compared to non-stimulated MΦ (M0-MΦ).
Mentions: Once the M0-MΦ capacity to interact and internalize N. gonorrhoeae is confirmedwe evaluated several M1 and M2-MФ-associated markers by flow cytometry 24 hours post N. gonorrhoeae exposure. Stimulation with N. gonorrhoeae increased the expression of the M2-MФ-associated marker CD163 at all the MOIs tested. CD206 M2-MФ-associated marker, in contrast, was only increased at MOI 1000 (Fig 2).

Bottom Line: Until now there are no reports of the gonococcus effects on human MФ polarization.Moreover, functional results showed that N. gonorrhoeae-treated MФ are unable to induce proliferation of human T-cells, suggesting a more likely regulatory phenotype.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.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología. Universidad de Chile, Santiago, Chile.

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.

No MeSH data available.


Related in: MedlinePlus