Affiliation:
1. Department of Molecular Biology and Biochemistry
2. Department of Pathology and Laboratory Medicine, University of California at Irvine College of Medicine, Irvine, California
3. Center for Immunology, University of California, Irvine, California
Abstract
ABSTRACT
The expression of chemokines within the heart during experimental infection of susceptible mice with the Colombiana strain of
Trypanosoma cruzi
was characterized in an attempt to determine a functional role for these molecules in both host defense and disease. Analysis of chemokine transcripts revealed that CXC chemokine ligand 9 (CXCL9) and CXCL10, as well as CC chemokine ligand 2 (CCL2) and CCL5, were prominently expressed during acute disease, whereas transcripts for CXCL9, CXCL10, and CCL5 remained elevated during chronic infection. Inflammatory macrophages present within the heart were the primary cellular source of these chemokines following
T. cruzi
infection. Peak chemokine expression levels coincided with increased gamma interferon expression and inflammation within the heart, suggesting a role for these molecules in both host defense and disease. Indeed, simultaneous treatment of
T. cruzi
-infected mice with neutralizing antibodies specific for CXCL9 and CXCL10 resulted in an increased parasite burden that was sustained out to 50 days p.i. Antibody targeting either CXCL10 or CCL5 did not change either
T. cruzi
burden within the heart nor attenuate the severity of cardiac inflammation at any time point examined, while targeting CXCL9 in combination with CXCL10 resulted in increased parasite burden. Collectively, these studies imply that CXCL9 and CXCL10 signaling enhances immune responses following parasite infection. However, antibody targeting of CXCL9 and CXCL10, or CXCL10 alone, or CCL5 alone does not directly modulate the inflammatory response within the heart, suggesting that other proinflammatory factors are able to regulate inflammation in this tissue in response to
T. cruzi
infection.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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