Human cytomegalovirus and Epstein-Barr virus inhibit oral bacteria-induced macrophage activation and phagocytosis.
BACKGROUND
Periodontal disease is an inflammatory condition caused by periodontal microorganisms. Viruses such as human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) are associated with certain types of periodontal disease, but their roles in promoting the disease are unclear. Because both viruses infect human macrophages, cells which play key roles in the clearance of pathogenic bacteria, it is likely that the viruses alter the functional capacity of macrophages by inhibiting their defense mechanisms against invading pathogens.


METHODS
Macrophages preinfected with HCMV or EBV were evaluated following stimulation by selected oral bacteria. Bacteria-induced macrophage activation was assayed by measuring the levels of tumor necrosis factor-alpha (TNF-alpha) produced in the media, and phagocytic activity was analysed by a phagocytosis assay with fluorescein isothiocyanate-labeled bacteria. The virus-infected macrophages were also subjected to semi-quantitative polymerase chain reaction to measure the expression of toll-like receptor 9, which is involved in the activation of phagocytosis-related pathways.


RESULTS
Both HCMV and EBV significantly diminished the TNF-alpha production typically induced by oral bacteria, inhibited the phagocytic activity of macrophages, and downregulated the expression of toll-like receptor 9.


CONCLUSIONS
Infection by HCMV or EBV inhibits the functional ability of macrophages to respond to bacterial challenge, thereby suggesting their pathogenic role in the development of periodontal disease.
Department of Oral Health Research, University of Kentucky College of Dentistry, Lexington, KY, USA.
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D016976:Aggregatibacter actinomycetemcomitans / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000502:physiology*; D015536:Down-Regulation; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D016967:Fusobacterium nucleatum / Q000502:physiology; D006090:Gram-Negative Bacteria / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000382:microbiology / Q000821:virology*; D009055:Mouth / Q000382:microbiology*; D010587:Phagocytosis / Q000502:physiology*; D016133:Polymerase Chain Reaction; D016966:Porphyromonas gingivalis / Q000502:physiology; D054773:Streptococcus gordonii / Q000502:physiology; D051217:Toll-Like Receptor 9 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D005456:Fluorescent Dyes; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D016650:Fluorescein-5-isothiocyanate