Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China.
Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China.
Int Immunopharmacol. 2022 Jun;107:108657. doi: 10.1016/j.intimp.2022.108657. Epub 2022 Feb 28.
Despite the acknowledged central role of opsonophagocytosis in the process of syphilis, the interaction between Treponema pallidum and human macrophages during nonopsonophagocytosis and active invasion remains controversial. To investigate whether nonopsonic phagocytosis and active invasion, similar to opsonic phagocytosis, also participate in the process of macrophage-T. pallidum interactions, monocyte-derived macrophages were used to study the interactions of T. pallidum and macrophages in the presence of nonsyphytic or syphilitic serum and in the absence of serum in vitro using indirect immunofluorescence and flow cytometry to quantitate treponeme-macrophage interactions. The results showed that macrophages phagocytose T. pallidum under both nonopsonizing conditions (no serum or normal human serum (NHS)) and in the presence of opsonizing serum (secondary syphilitic serum (SSS)) in a time-dependent manner. The percentages of spirochete-positive macrophages in the SSS group were higher than those in the NHS and no-serum groups. Blocking FcγR or inactivating complement caused a significant decrease in the percentage of spirochete-positive macrophages in the SSS group but did not cause a decrease in the percentages of spirochete-positive macrophages in the NHS and no-serum groups. In addition, after inhibiting macrophage phagocytosis, approximately 30% of macrophages internalized spirochetes, verifying that T. pallidum actively penetrated macrophages rather than was ingested by them. This study provides evidence that opsonic phagocytosis, nonopsonic phagocytosis and active invasion are all active during T. pallidum-macrophage interactions and reveals a process of treponeme-macrophage interactions in T. pallidum pathogenesis.
尽管补体调理吞噬作用在梅毒发病机制中起重要作用，但苍白密螺旋体与人类巨噬细胞在非调理吞噬作用和主动侵袭过程中的相互作用仍存在争议。为了研究非调理吞噬作用和主动侵袭作用是否与调理吞噬作用相似，也参与巨噬细胞-苍白密螺旋体相互作用的过程，本研究使用单核细胞来源的巨噬细胞，在体外使用间接免疫荧光和流式细胞术来定量苍白密螺旋体-巨噬细胞相互作用，研究无梅毒或梅毒患者血清存在时，以及无血清情况下，苍白密螺旋体与巨噬细胞的相互作用。结果表明，巨噬细胞在非调理条件（无血清或正常人血清（NHS））和调理血清（二期梅毒血清（SSS））存在的情况下，均能以时间依赖的方式吞噬苍白密螺旋体。SSS 组中螺旋体阳性巨噬细胞的百分比高于 NHS 组和无血清组。阻断 FcγR 或使补体失活可显著降低 SSS 组中螺旋体阳性巨噬细胞的百分比，但不会降低 NHS 组和无血清组中螺旋体阳性巨噬细胞的百分比。此外，在抑制巨噬细胞吞噬作用后，约 30%的巨噬细胞内化了螺旋体，证实了苍白密螺旋体主动穿透巨噬细胞，而不是被巨噬细胞吞噬。本研究为调理吞噬作用、非调理吞噬作用和主动侵袭作用在苍白密螺旋体-巨噬细胞相互作用过程中均为活跃状态提供了证据，并揭示了苍白密螺旋体发病机制中螺旋体-巨噬细胞相互作用的过程。
