The Major Outer Membrane Protein of a Periodontopathogen Induces IFN-β and IFN-Stimulated Genes in Monocytes via Lipid Raft and TANK-Binding Kinase 1/IFN Regulatory Factor-3

Abstract

Surface molecules of pathogens play an important role in stimulating host immune responses. Elucidation of the signaling pathways activated by critical surface molecules in host cells provides insight into the molecular pathogenesis resulting from bacteria-host interactions. MspTL is the most abundant outer membrane protein of Treponema lecithinolyticum, which is associated with periodontitis, and induces expression of a variety of proinflammatory factors. Although bacteria and bacterial components like LPS and flagellin are known to induce IFN-β, induction by bacterial surface proteins has not been reported. In the present study, we investigated MspTL-mediated activation of signaling pathways stimulating up-regulation of IFN-β and IFN-stimulated genes in a human monocytic cell line, THP-1 cells, and primary cultured human gingival fibroblasts. MspTL treatment of the cells induced IFN-β and the IFN-stimulated genes IFN-γ-inducible protein-10 (IP-10) and RANTES. A neutralizing anti-IFN-β Ab significantly reduced the expression of IP-10 and RANTES, as well as STAT-1 activation, which was also induced by MspTL. Experiments using specific small interfering RNA showed that MspTL activated TANK-binding kinase 1 (TBK1), but not inducible IκB kinase (IKKi). MspTL also induced dimerization of IFN regulatory factor-3 (IRF-3) and translocation into the nucleus. The lipid rapid-disrupting agents methyl-β-cyclodextrin, nystatin, and filipin inhibited the MspTL internalization and cellular responses, demonstrating that lipid raft activation was a prerequisite for MspTL cellular signaling. Our results demonstrate that MspTL, the major outer protein of T. lecithinolyticum, induced IFN-β expression and subsequent up-regulation of IP-10 and RANTES via TBK1/IRF-3/STAT-1 signaling secondary to lipid raft activation.

Involvement of caveolin-1 in the Jak–Stat signaling pathway and infectious spleen and kidney necrosis virus infection in mandarin fish (Siniperca chuatsi)

“…These results were consistent with the typical distribution of caveolin-1 in mammalian cells (Parkin et al, 1996). M␤CD, fillipin III, or nystatin (which deplete or sequester membrane cholesterol) is employed to disrupt the caveolae structure (Foster et al, 2003;Lee et al, 2008Lee et al, , 2009. As shown in Fig.…”

Human B1 Cell Frequency: Isolation and Analysis of Human B1 Cells

“…This has led to intense interest in the physiological and clinical roles of B1 cells, which, however, have been difficult to evaluate because clear markers for the human B1 cell population have been lacking for many years. Early efforts to identify human B1 cells using CD5 expression combined with expression of a B cell specific antigen, as in the murine system, have not been revealing because CD5 is expressed on multiple human B cell populations including activated, pre-naïve, and transitional B cells (Freedman et al, 1989; Sims et al, 2005; Lee et al, 2009a; Griffin et al, 2011a). …”

Enhancing Specific-Antibody Production to the ragB Vaccine with GITRL That Expand Tfh, IFN-γ+ T Cells and Attenuates Porphyromonas gingivalis Infection in Mice

“…Our findings strongly indicated that pIRES- ragB-mGITRL may become a potential candidate of DNA vaccine for inhibiting P. gingivalis infection, and GITRL may be a new type of adjuvant (Figure 7). Further studies will focus on how RagB regulates cytokines production in mice, via lipid raft or the surface receptor of innate immunity cells, like the major outer membrane protein of a periodontopathogen, Treponema lecithinolyticum [47], and whether the action of RagB and mGITRL can be blocked by anti-serum from the mice injected with pIRES- ragB-mGITRL .…”