Cyclooxygenase-2 Inhibition Enhances Activation of T Helper Type 1 Responses During Salmonella Infection

Abstract

Production of IL-12 and IFN-γ secretion are important components of the protective host response against the intracellular bacterial pathogen, Salmonella typhimurium. While infection with Salmonella does elicit this T helper type 1 response, its magnitude does not appear to be sufficient to prevent infection or limit pathogenesis. Therefore we have investigated factors which might limit a T helper type 1 response following infection. Previously we found that infection of antigen presenting cells with Salmonella dramatically increases cyclooxygenase-2 (COX-2) activity, resulting in high levels of prostaglandin E₂ (PGE₂). Since PGE₂ production can have profound effects on initiation of T helper type 1 responses, we questioned whether this mediator might limit antigen-specific T cell activation. Here we show that blockage of COX-2 activity with the selective inhibitor celecoxib leads to enhancement of the T helper type 1 components stimulated by Salmonella infection. In vitro studies demonstrate the induction of IL-12 and IFN-γ upon Salmonella exposure, which are further increased following COX-2 inhibition. Taken together these in vitro studies suggest that COX-2 activity can limit a salmonella-initiated T helper type 1 response.