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Infection and Immunity, April 1999, p. 1547-1552, Vol. 67, No. 4
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Chemokine Secretion of Human Cells in Response to Toxoplasma gondii Infection

Carolyn F. Denney,1 Lars Eckmann,1 and Sharon L. Reed1,2,*

Departments of Medicine1 and Pathology,2 University of California, San Diego, San Diego, California 92103-8416

Received 12 August 1998/Returned for modification 16 September 1998/Accepted 5 January 1999

The ubiquitous protozoan parasite Toxoplasma gondii is a major cause of morbidity and mortality in neonates and immunocompromised hosts. Both acute invasion and reactivation of latent infection result in an inflammatory reaction with lymphocytes, macrophages, and neutrophils. The mechanisms responsible for triggering the local host response to toxoplasmosis are not fully understood. Infection of monolayers of human HeLa epithelial cells and fibroblasts with T. gondii resulted in a marked increase in the expression of interleukin-8 (IL-8)-specific mRNA and secretion of the proinflammatory and chemoattractant cytokines interleukin-8 (IL-8), GROalpha , and MCP-1. Host cell invasion and lysis were required for this response, as tachyzoite lysates alone had no effect on IL-8 secretion. IL-8 release was dependent on the release of soluble host cell factors: IL-1alpha in HeLa cells and an additional mediator in fibroblasts. HT-29 epithelial cells, which lack IL-1alpha 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-1alpha . These data suggest that proinflammatory chemokine secretion is an important host cell response to toxoplasmosis and that the release of IL-1alpha and other mediators from lysed host cells is critical for this chemokine response.


* Corresponding author. Mailing address: Division of Infectious Diseases, UCSD Medical Center, 200 W. Arbor Dr., San Diego, CA 92103-8416. Phone: (619) 543-6146. Fax: (619) 543-6614. E-mail: slreed{at}popmail.ucsd.edu.


Infection and Immunity, April 1999, p. 1547-1552, Vol. 67, No. 4
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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