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Autophagy promotes phagocytosis and clearance of Treponema pallidum via the NLRP3 inflammasome in macrophages
Author(s) -
Xu S.L.,
Lin Y.,
Zhu X.Z.,
Liu D.,
Tong M.L.,
Liu L.L.,
Yang T.C.,
Lin L.R.
Publication year - 2020
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1111/jdv.16463
Subject(s) - phagocytosis , autophagy , macrophage , inflammasome , internalization , treponema , gene silencing , medicine , microbiology and biotechnology , immunology , chemistry , biology , in vitro , inflammation , receptor , gene , apoptosis , biochemistry , syphilis , human immunodeficiency virus (hiv)
Background Elucidating the mechanism of the macrophage phagocytic response will improve our knowledge of host defence against Treponema pallidum . Objective To explore whether autophagy promotes T. pallidum phagocytosis and clearance via the NLRP3 inflammasome in macrophages. Methods The interactions between autophagy and phagocytosis and the role of NLRP3 in these processes in T. pallidum ‐treated macrophages were investigated through experiments using human monocytic cell line (THP‐1)‐derived macrophages. Treponema pallidum clearance after phagocytosis was evaluated by inoculating rabbits with macrophage–treponeme mixtures. Results Activation of autophagy and phagocytosis in T. pallidum‐ treated macrophages occurred in a dose‐ and time‐dependent manner. The percentage of spirochete‐positive macrophages (22.34% vs. 70.93%, P < 0.001) and spirochete internalization (MFI: 9.62 vs. 20.33, P < 0.001) were notably reduced by silencing Beclin1 . Inoculation of macrophage–treponeme mixtures into rabbits showed a 3.00‐day delay in lesion development (17.55 ± 3.73 vs. 14.55 ± 1.99 days) and decreased lesion numbers [11 (36.7%) vs. 20 (66.7%) of 30; χ 2 = 5.406, P = 0.020] in the control compared with the si‐ Beclin1 group. Furthermore, silencing NLRP3 decreased the mRNA and protein levels of Beclin‐1 and LC3B [mRNA: 49.86% and 43.02%; protein: 22.31% and 24.24%, respectively, differing significantly from the control group ( P < 0.001)] and reduced the percentage of spirochete‐positive macrophages (30.29% vs. 70.53%, P < 0.001) and spirochete internalization (MFI: 9.82 vs. 19.33, P < 0.001). Conclusion Treponema pallidum induces autophagy in macrophages to promote phagocytosis and clearance. The NLRP3 inflammasome modulates autophagy and phagocytosis in vitro . These data may be useful for understanding the host–pathogen relationship and establish the groundwork for strategies to combat syphilis.