Wednesday, January 16, 2008

Co-infection with Heligmosomoides polygyrus fails to establish a CD8+ T cell immunity against Toxo

Infect Immun. 2008 Jan 14 [Epub ahead of print]

Co-infection with Heligmosomoides polygyrus fails to establish a CD8+ T cell immunity against Toxoplasma gondii

Khan IA, Hakak R, Eberle K, Sayles P, Weiss LM, Urban JF Jr.

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

CD8(+) T cell immunity is important for long-term protection against Toxoplasma gondii infection. However, a Th1 cytokine environment, especially the presence of IFNgamma, 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 IFNgamma 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 dual infected mice. At the later stages, however, T. gondii-specific CD4(+) T cell immunity recovered, while CD8(+) T cell responses remained low. Unlike mice infected with T. gondii alone, depletion of CD4(+) T cells in the dual 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 co-infection model that has important implications for infections where a CD8(+) T cell response is critical for host protection and reduced infection pathology.

PMID: 18195022 [PubMed - as supplied by publisher]

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