Monocyte suppression of Fusobacterium nucleatum-induced human polyclonal B-lymphocyte activation

Abstract

Previous studies reported that Fusobacterium nucleatum induced polyclonal B-lymphocyte activation (PBA) as determined by immunoglobulin M production in cultures of human peripheral blood mononuclear cells. However, the PBA response was greatly enhanced when the cells were depleted of esterase-positive, adherent cells (i.e., monocytes). The purpose of this study was to confirm and further examine the suppression of F. nucleatum-induced PBA (F. nucleatum-PBA) by blood monocytes. For comparison, PBA induced by pokeweed mitogen (PWM-PBA), which is enhanced by monocytes, was assessed in some experiments. We found the removal of monocytes from unfractionated cells by (i) Sephadex G-10, (ij) anti-monocyte specific OM-1 monoclonal antibody plus complement, or (iii) L-leucine methyl ester, a compound which selectively kills lysosome-rich cells, resulted in a population of cells responsive to F. nucleatum-PBA and unresponsive to PWM-PBA. The addition of double adherence-purified monocytes (>85% esterase-positive cells), particularly in concentrations of >10%, to lymphocytes depleted of monocytes by G-10, OM-1, or L-leucine methyl ester treatments, suppressed F. nucleatum-PBA and enhanced PWM-PBA. Monocytes also suppressed a mixture of isolated T and B cells combined in a T/B cell ratio of 3:1, which is an optimal ratio for F. nucleatum-PBA. Allogeneic monocytes suppressed F. nucleatum-PBA, although at low numbers these cells were not as

Taxonomy, biology, and periodontal aspects of Fusobacterium nucleatum.

“…Such a model may explain the contradictory clinical observations of the host immune response to oral pathogens and its correlation or lack of correlation with progression and severity of periodontal disease. This model is consistent with the finding that several suspected periodontal pathogens are capable of producing immunosuppressive factors (195,257,258). F. nucleatum produces factors capable of suppressing lymphocyte responses in vitro (258).…”

“…Monocyte suppression of F. nucleatum-induced human polyclonal B-lymphocyte activation demonstrates a potent mechanism by which the host might prevent exaggerated nonspecific immunoglobulin responses when exposed to polyclonal B-lymphocyte-inducing activities of F. nucleatum. On the other hand, the induction of suppressive monocytes by F. nucleatum may result in the inhibition of host-protective immune reactions (195). Local suppression of specific antibody production by F. nucleatum may be the reason why Hall et al (116) found immunoglobulins to this bacterium in supernatant fluid from juvenile periodontitis tissues in only 1 of 75 patients, even though this microorganism is often isolated from subgingival plaque of such patients and F. nucleatum-specific antibodies have been detected in their sera (203,314).…”

Antibody synthesis specific for nonoral antigens in inflamed gingiva

“…To investigate this possibility, PBL were taken from hyperimmunized rabbits immediately before and 7 days after booster immunization. These cells were cultured for 12 days without stimulant or with an extract of F. nucleatum, a periodontitis-associated bacterium which is a potent polyclonal B-cell stimulator in the human PBL system (15)(16)(17). Supernatants from these cell cultures were assayed for specific antibody production (Table 2).…”

Induction of systemic murine B‐cell responses by Fusobacterium nucleatum and Porphyromonas gingivalis

“…The presence of monocytes in cell culture has been shown to suppress the polyclonal B-cell activation-effect induced by F. nucleatum, when monocytes were present in the cell culture on the first 2 days (29). In the present study, the cell suspension obtained from the mouse spleens contained a mixture of mononuclear cells.…”