Ehrlichia chaffeensis is an obligatory intracellular bacterium that infects monocytes and macrophages and is the etiologic agent of
human ehrlichiosis in the United States. Our previous studies showed that the exposure of human monocytes to E. chaffeensis induces the expression of
interleukin-1beta (IL-1beta),
IL-8, and
IL-10 genes in vitro but not the expression of
tumor necrosis factor alpha (
TNF-alpha) and
IL-6 mRNAs. In this study, the effect of anti-E. chaffeensis antibody complexed with E. chaffeensis on the expression of major proinflammatory
cytokines in human monocytes was examined. Human monocytic cell line THP-1 was treated with E. chaffeensis which had been preincubated with human anti-E. chaffeensis serum for 2 h, and the levels of
cytokine mRNAs were evaluated by competitive reverse transcription-PCR. Anti-E. chaffeensis antibody complexed with E. chaffeensis significantly enhanced
mRNA expression of IL-1beta in THP-1 cells. The expression of
TNF-alpha and
IL-6 mRNAs was also induced. The levels of secreted IL-1beta,
TNF-alpha, and
IL-6 during 24 h of stimulation were comparable to those induced by Escherichia coli
lipopolysaccharide at 1 microg/ml.
Fab fragment of anti-E. chaffeensis
immunoglobulin G complexed with E. chaffeensis did not induce any of these three
cytokines, indicating that ehrlichial binding is required for IL-1beta
mRNA expression and that binding of the
immune complex to the
Fc gamma receptor is required for
TNF-alpha and
IL-6 mRNA expression and enhanced IL-1beta
mRNA expression. Furthermore, prolonged degradation of
IkappaB-alpha and activation of
NF-kappaB were demonstrated in THP-1 cells exposed to anti-E. chaffeensis serum and E. chaffeensis. This result implies that development of anti-E. chaffeensis antibody in patients can result in the production of major proinflammatory
cytokines, which may play an important role in the pathophysiology of
ehrlichiosis and immune responses to it.