Autophagy promotes phagocytosis and clearance of Treponema pallidum via the NLRP3 inflammasome in macrophages.

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; χ2  = 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.