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Infection and Immunity, January 2005, p. 181-192, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.181-192.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Critical Proinflammatory and Anti-Inflammatory Functions of Different Subsets of CD1d-Restricted Natural Killer T Cells during Trypanosoma cruzi Infection

Malcolm S. Duthie,1 Maria Kahn,1 Maria White,1 Raj P. Kapur,2 and Stuart J. Kahn1*

Infectious Disease Research Institute,1 Department of Pathology, Children's Hospital and Regional Medical Center, Seattle, Washington2

Received 1 July 2004/ Returned for modification 20 August 2004/ Accepted 6 September 2004

Trypanosoma cruzi infects 15 to 20 million people in Latin America and causes Chagas disease, a chronic inflammatory disease with fatal cardiac and gastrointestinal sequelae. How the immune response causes Chagas disease is not clear, but during the persistent infection both proinflammatory and anti-inflammatory responses are critical. Natural killer T (NKT) cells have been shown to regulate immune responses during infections and autoimmune diseases. We report here that during acute T. cruzi infection NKT-cell subsets provide distinct functions. CD1d–/– mice, which lack both invariant NKT (iNKT) cells and variant NKT (vNKT) cells, develop a mild phenotype displaying an increase in spleen and liver mononuclear cells, anti-T. cruzi antibody response, and muscle inflammation. In contrast, J{alpha}18–/– mice, which lack iNKT cells but have vNKT cells, develop a robust phenotype involving prominent spleen, liver, and skeletal muscle inflammatory infiltrates comprised of NK, dendritic, B and T cells. The inflammatory cells display activation markers; produce more gamma interferon, tumor necrosis factor alpha, and nitric oxide; and show a diminished antibody response. Strikingly, most J{alpha}18–/– mice die. Thus, in response to the same infection, vNKT cells appear to augment a robust proinflammatory response, whereas the iNKT cells dampen this response, possibly by regulating vNKT cells.

* Corresponding author. Mailing address: IDRI, 1124 Columbia St., Ste. 600, Seattle, WA 98104. Phone: (206) 381-0883. Fax: (206) 381-3678. E-mail: skahn{at}idri.org.

Editor: W. A. Petri, Jr.

Infection and Immunity, January 2005, p. 181-192, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.181-192.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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