AUTHOR=Fan Xiaomiao , Zheng Shaowen , Chen Chen , Lin Li , Wang Hongyan , Shen Yuqin , Pan Yaping , Li Chen 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1173899

DOI=10.3389/fcimb.2023.1173899

ISSN=2235-2988

ABSTRACT=<sec><title>Background</title><p><italic>Porphyromonas gingivalis</italic> (<italic>P. gingivalis</italic>), a major pathogen of periodontitis, can evade host immune defenses. Previously, we found that <italic>P. gingivalis</italic> 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 <italic>P. gingivalis</italic> on the polarization, antigen presentation, and phagocytosis of infected macrophages and to clarify the mechanism of <italic>P. gingivalis</italic> immune evasion.</p></sec><sec><title>Methods</title><p>Human monocytes U937 were differentiated to macrophages and infected with <italic>P. gingivalis</italic> W83, ΔPG0352, comΔPG0352, and <italic>Escherichia coli</italic> (<italic>E. coli</italic>). 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.</p></sec><sec><title>Results</title><p>Compare with <italic>P. gingivalis</italic> 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 <italic>P. gingivalis</italic> W83. In the rat periodontitis model, the levels of M1 and M2 macrophages in <italic>P. gingivalis</italic> 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.</p></sec><sec><title>Conclusion</title><p>Sialidase facilitates <italic>P. gingivalis</italic> immune evasion by reducing M1 polarization, antigen presentation, and phagocytosis of infected macrophages.</p></sec>