Human polymorphonuclear leukocytes produce IL-12, TNF-alpha, and the chemokines macrophage-inflammatory protein-1 alpha and-1 beta in response to Toxoplasma gondii antigens

The induction of a type 1 inflammatory cytokine response is a key event in the initiation of immunity to Toxoplasma gondii, Because polymorphonuclear leukocytes rapidly respond to infection by exiting the peripheral blood and accumulating at a site of infection, we sought to determine whether these cells produce cytokines in response to T. gondii, When human peripheral blo od neutrophils were stimulated with parasite Ag, they produced both IL-12 ( p70) and TNF-alpha. Similarly, up-regulated expression of macrophage-inflam matory protein-1 alpha (MIP-1 alpha) and MIP-1 beta gene transcripts was in duced. Kinetic analysis of IL-12 and TNF-alpha production revealed distinct patterns following stimulation by T. gondii or LPS, Exogenous TNF-alpha al one also provided a potent stimulus of MIP-1 alpha and MIP-1 beta expressio n, and when neutralizing anti-TNF-alpha antiserum was included in cultures of parasite-stimulated cells, expression of these CC-family chemokines was partially blocked. These results establish that T. gondii possesses the abi lity of driving neutrophil proinflammatory cytokine production, and they su ggest that parasite-induced MIP-1 alpha and MIP-1 beta partly results from autocrine stimulation through TNF-alpha.