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, and the Chemokines Macrophage-Inflammatory Protein-1 and -1ß in Response to Toxoplasma gondii Antigens1
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
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 blood
neutrophils were stimulated with parasite Ag, they produced both IL-12
(p70) and TNF-
. Similarly, up-regulated expression of
macrophage-inflammatory protein-1 (MIP-1) and MIP-1ß gene
transcripts was induced. Kinetic analysis of IL-12 and TNF-
production revealed distinct patterns following stimulation by
T. gondii or LPS. Exogenous TNF- alone also provided
a potent stimulus of MIP-1 and MIP-1ß expression, and when
neutralizing anti-TNF- 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 ability of driving neutrophil
proinflammatory cytokine production, and they suggest that
parasite-induced MIP-1 and MIP-1ß partly results from autocrine
stimulation through TNF-.
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