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Infection and Immunity, March 2008, p. 1305-1313, Vol. 76, No. 3
0019-9567/08/$08.00+0     doi:10.1128/IAI.01236-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Coinfection with Heligmosomoides polygyrus Fails To Establish CD8+ T-Cell Immunity against Toxoplasma gondii{triangledown}

Imtiaz A. Khan,1* Rubeena Hakak,2 Karen Eberle,2 Peter Sayles,3 Louis M. Weiss,4 and Joseph F. Urban Jr.5

Department of Microbiology and Tropical Medicine and Immunology, George Washington University, Washington, DC 20037,1 Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112,2 Trudeau Institute, Saranac Lake, New York 12983,3 Department of Medicine and Pathology, Albert Einstein College of Medicine, Bronx, New York 10461,4 USDA/ARS/Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, Maryland 207055

Received 7 September 2007/ Returned for modification 4 October 2007/ Accepted 7 January 2008

CD8+ T-cell immunity is important for long-term protection against Toxoplasma gondii infection. However, a Th1 cytokine environment, especially the presence of gamma interferon (IFN-{gamma}), is essential for the development of primary CD8+ T-cell immunity against this obligate intracellular pathogen. Earlier studies from our laboratory have demonstrated that mice lacking optimal IFN-{gamma} levels fail to develop robust CD8+ T-cell immunity against T. gondii. In the present study, induction of primary CD8+ T-cell immune response against T. gondii infection was evaluated in mice infected earlier with Heligmosomoides polygyrus, a gastrointestinal worm known to evoke a polarized Th2 response in the host. In the early stage of T. gondii infection, both CD4 and CD8+ T-cell responses against the parasite were suppressed in the dually infected mice. At the later stages, however, T. gondii-specific CD4+ T-cell immunity recovered, while CD8+ T-cell responses remained low. Unlike in mice infected with T. gondii alone, depletion of CD4+ T cells in the dually infected mice led to reactivation of chronic infection, leading to Toxoplasma-related encephalitis. Our observations strongly suggest that prior infection with a Th2 cytokine-polarizing pathogen can inhibit the development of CD8+ T-cell immune response against T. gondii, thus compromising long-term protection against a protozoan parasite. This is the first study to examine the generation of CD8+ T-cell immune response in a parasitic nematode and protozoan coinfection model that has important implications for infections where a CD8+ T-cell response is critical for host protection and reduced infection pathology.

* Corresponding author. Mailing address: Department of Microbiology and Tropical Medicine and Immunology, George Washington University, Washington, DC 20037. Phone: (202) 994-2863. Fax: (202) 994-2913. E-mail: mtmixk{at}gwumc.edu

{triangledown} Published ahead of print on 14 January 2008.

Editor: W. A. Petri, Jr.

Infection and Immunity, March 2008, p. 1305-1313, Vol. 76, No. 3
0019-9567/08/$08.00+0     doi:10.1128/IAI.01236-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Helmby, H. (2009). Gastrointestinal Nematode Infection Exacerbates Malaria-Induced Liver Pathology. J. Immunol. 182: 5663-5671 [Abstract] [Full Text]  
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