Sialidase facilitates Porphyromonas gingivalis immune evasion by reducing M1 polarization, antigen presentation, and phagocytosis of infected macrophages

Xiaomiao Fan; Shaowen Zheng; Chen Chen; Li Lin; Hongyan Wang; Yuqin Shen; Yaping Pan; Chen Li

doi:10.3389/fcimb.2023.1173899

Sialidase facilitates Porphyromonas gingivalis immune evasion by reducing M1 polarization, antigen presentation, and phagocytosis of infected macrophages

Front Cell Infect Microbiol. 2023 May 30:13:1173899. doi: 10.3389/fcimb.2023.1173899. eCollection 2023.

Authors

Xiaomiao Fan^{1

2}, Shaowen Zheng¹, Chen Chen¹, Li Lin¹, Hongyan Wang¹, Yuqin Shen², Yaping Pan¹, Chen Li¹

Affiliations

¹ Department of Periodontology, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease, Shenyang, Liaoning, China.
² Department of Periodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, China.

Abstract

Background: Porphyromonas gingivalis (P. gingivalis), a major pathogen of periodontitis, can evade host immune defenses. Previously, we found that P. gingivalis W83 sialidase gene mutant strain (ΔPG0352) was more easily cleared by macrophages. The aims of this study were to investigate the effects of sialidase in P. gingivalis on the polarization, antigen presentation, and phagocytosis of infected macrophages and to clarify the mechanism of P. gingivalis immune evasion.

Methods: Human monocytes U937 were differentiated to macrophages and infected with P. gingivalis W83, ΔPG0352, comΔPG0352, and Escherichia coli (E. coli). The phagocytosis of macrophages was observed by transmission electron microscopy and flow cytometry. ELISA or Griess reaction were used to examine the levels of interleukin-12 (IL-12), inducible nitric oxide synthase (iNOS) and interleukin-10 (IL-10), and the expressions of CD68, CD80 and CD206 were determined by flow cytometry. The expression of major histocompatibility complex-II (MHC-II) was detected by immunofluorescence. A rat periodontitis model was established to determine the M1 and M2 polarization of macrophages.

Results: Compare with P. gingivalis W83, ΔPG0352 increased the levels of IL-12, iNOS, CD80, and MHC-II and inhibited the levels of IL-10 and CD206. Macrophages phagocytosed 75.4% of ΔPG0352 and 59.5% of P. gingivalis W83. In the rat periodontitis model, the levels of M1 and M2 macrophages in P. gingivalis W83 group were both higher than those in ΔPG0352 group, while the ratio of M1/M2 was higher in the ΔPG0352 group. Alveolar bone absorption was lower in ΔPG0352 group.

Conclusion: Sialidase facilitates P. gingivalis immune evasion by reducing M1 polarization, antigen presentation, and phagocytosis of infected macrophages.

Keywords: Porphyromonas gingivalis; macrophage; periodontitis; polarization; sialidase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigen Presentation
Escherichia coli / metabolism
Humans
Immune Evasion
Interleukin-10* / metabolism
Interleukin-12 / metabolism
Macrophages
Neuraminidase / metabolism
Periodontitis* / metabolism
Phagocytosis
Porphyromonas gingivalis / genetics
Rats

Substances

Interleukin-10
Neuraminidase
Interleukin-12

Grants and funding

This work was supported by National Natural Science Foundation of China (grant number 81800974), Youth Science and Technology Talent “Bringing Seedlings” Project of Liaoning Provincial Department of Education (grant number QN20190120) and Natural Science Foundation of Liaoning Province, Liaoning, China (grant number 2019-ZD-0760).