Immune response profiling of primary monocytes and oral keratinocytes to different Tannerella forsythia strains and their cell surface mutants

Summary

The oral pathogen Tannerella forsythia possesses a unique surface (S-) layer with a complex O-glycan containing a bacterial sialic acid mimic in the form of either pseudaminic acid or legionaminic acid at its terminal position. We hypothesize that different T. forsythia strains employ these stereoisomeric sugar acids for interacting with the immune system and resident host tissues in the periodontium. Here, we show how T. forsythia strains ATCC 43037 and UB4, displaying pseudaminic acid and legionaminic acid, respectively, and selected cell surface mutants of these strains, modulate the immune response in monocytes and human oral keratinocytes (HOK) using a multiplex immunoassay. When challenged with T. forsythia, monocytes secrete pro-inflammatory cytokines, chemokines and VEGF with the release of IL-1β and IL-7 being differentially regulated by the two T. forsythia wild-type strains. Truncation of the bacteria's O-glycan leads to significant reduction of IL-1β and regulates MIP-1. HOK infected with T. forsythia produce IL-1Ra, chemokines and VEGF. While the two wild-type strains elicit preferential immune responses for IL-8, both truncation of the O-glycan and deletion of the S-layer results in significantly increased release of IL-8, GM-CSF and MCP-1. Through immunofluorescence and confocal laser scanning microscopy of infected HOK we additionally show that T. forsythia is highly invasive and tends to localize to the perinuclear region. This indicates, that the T. forsythia S-layer and attached sugars, particularly pseudaminic acid in ATCC 43037, contribute to dampening the response of epithelial tissues to initial infection and, therefore, play a pivotal role in orchestrating the bacterium's virulence.

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