G. Telford et al., THE PSEUDOMONAS-AERUGINOSA QUORUM-SENSING SIGNAL MOLECULE N-(3-OXODODECANOYL)-1-HOMOSERINE LACTONE HAS IMMUNOMODULATORY ACTIVITY, Infection and immunity, 66(1), 1998, pp. 36-42
Diverse gram-negative bacterial cells communicate with each other by u
sing diffusible N-acyl homoserine lactone (AHL) signal molecules to co
ordinate gene expression with cell population density. Accumulation of
AHLs above a threshold concentration renders the population ''quorate
,'' and the appropriate target gene is activated. In pathogenic bacter
ia, such as Pseudomonas aeruginosa, AHL-mediated quorum sensing is inv
olved in the regulation of multiple virulence determinants, We therefo
re sought to determine whether the immune system is capable of respond
ing to these bacterial signal molecules, Consequently the immunomodula
tory properties of the AHLs N-(3-oxododecanoyl)-L-homoserine lactone (
OdDHL) and N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) were evaluate
d in murine and human leukocyte immunoassays in vitro. OdDHL, but not
OHHL, inhibited lymphocyte proliferation and tumor necrosis factor alp
ha production by lipopolysaccharide-stimulated macrophages. Furthermor
e, OdDHL simultaneously and potently down-regulated the production of
IL-12, a Th-1-supportive cytokine. At high concentrations (>7 x 10(-5)
M) OdDHL inhibited antibody production by keyhole limpet hemocyanin-s
timulated spleen cells, but at lower concentrations (<7 x 10(-5) M), a
ntibody production was stimulated, apparently by increasing the propor
tion of the immunoglobulin G1 (IgG1) isotype, OdDHL also promoted IgE
production by interleukin-4-stimulated human peripheral blood mononucl
ear cells, These data indicate that OdDHL mag influence the Th-1-Th-2
balance in the infected host and suggest that, in addition to regulati
ng the expression of virulence determinants, OdDHL may contribute to t
he pathogenesis of P. aeruginosa infections by functioning as a virule
nce determinant per se.