Translation of Oral-Systemic Inflammation. Key Signaling Mechanisms

The effect of organ-specific inflammation resulted from infection on remote organs was documented in animals and humans, but the mechanism involved is still not clear. Using a mice model we had found that P. gingivalis infection in subcutaneous chambers can aggravate the course of viral infections. We hypothesize that the mechanism involved is related to the effect of the remote infection on T-cell functions. T-cells harvested from mice after sustained exposure to P. gingivalis were unable to mount a normal cytotoxic reaction. Furthermore, the immediate T-cell receptor (TCR) mediated signaling events were impaired, but the downstream machinery worked properly. Immunoblots and confocal microscopy revealed that the ζ-chain of the TCR in down-regulated by chronic exposure to P. gingivalis. This down regulation was only observed after long-term exposure to the bacteria, and was depended on the development of Th1-response, particularly the presence of IFNγ. IFNγ indirectly affects the T cells through a non-T cell population that were recruited to the spleen during chronic inflammation. The inflammation-induced immunosuppressive environment was found to be present in the spleen, but not in the lymph nodes. ζ-chain down regulation could be a physiological response in chronic inflammation that attenuates an exacerbated immune response, but this can acts as a “double-edged sword”, impairing immune responses to systemic diseases.