The C ‐terminal region of the major outer sheath protein of Treponema denticola inhibits neutrophil chemotaxis

In this study, we investigated the inhibitory effect of truncated Msp regions on neutrophil chemotaxis and associated signaling pathways. Murine neutrophils were treated with recombinant protein truncations followed by assessment of chemotaxis and associated signal pathway activation. Chemotaxis assays indicate sequences within the C‐terminal region; particularly the first 130 amino acids, have the strongest inhibitory effect on neutrophil chemotaxis. Neutrophils incubated with the C‐terminal region protein also demonstrated the greatest inhibition of Rac1 activation, increased phosphoinositide phosphatase activity, and decreased Akt activation; orchestrating impairment of chemotaxis. Furthermore, incubation with antibodies specific to only the C‐terminal region blocked the Msp‐induced inhibition of chemotaxis and denaturing the protein restored Rac1 activation. Msp from the strain OTK, with numerous amino acid substitutions throughout the polypeptide, including the C‐terminal region compared with strain 35405, showed increased ability to impair neutrophil chemotaxis. Collectively, these results indicate that the C‐terminal region of Msp is the most potent region to modulate neutrophil chemotactic signaling and that specific sequences and structures are likely to be required. Knowledge of how spirochetes dampen the neutrophil response is limited and Msp may represent a novel therapeutic target for periodontal disease.
Source: Oral Microbiology and Immunology - Category: Microbiology Authors: Tags: ORIGINAL ARTICLE Source Type: research