Chemokine secretion of human cells in response to Toxoplasma gondii infection

The ubiquitous protozoan parasite Toxoplasma gondii is a major cause of mor bidity and mortality in neonates and immunocompromised hosts. Both acute in vasion and reactivation of latent infection result in an inflammatory react ion with lymphocytes, macrophages, and neutrophils. The mechanisms responsi ble for triggering the local host response to toxoplasmosis are not fully u nderstood. Infection of monolayers of human HeLa epithelial cells and fibro blasts with T. gondii resulted in a marked increase in the expression of in terleukin-1 (IL-8)-specific mRNA and secretion of the proinflammatory and c hemoattractant cytokines interleukin-8 (IL-8), GRO alpha, and MCP-1. Host c ell invasion and lysis were required for this response, as tachyzoite lysat es alone had no effect on IL-8 secretion. IL-8 release was dependent on the release of soluble host cell factors: IL-1 alpha in HeLa cells and an addi tional mediator in fibroblasts. HT-29 epithelial cells, which lack IL-1 alp ha or another IL-8-inducing activity, did not release IL-8 after infection, although they were efficiently infected with T. gondii and increased IL-8 secretion in response to added IL-1 alpha. These data suggest that proinfla mmatory chemokine secretion is an important host cell response to toxoplasm osis and that the release of IL-1 alpha and other mediators from lysed host cells is critical for this chemokine response.