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

• Published in: Infection and Immunity 2008-03, Vol.76 (3), p.1305-1313
• Main Authors: Khan, Imtiaz A, Hakak, Rubeena, Eberle, Karen, Sayles, Peter, Weiss, Louis M, Urban, Joseph F. Jr
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; CD4-positive T-lymphocytes; CD4-Positive T-Lymphocytes - immunology; CD8-positive T-lymphocytes; CD8-Positive T-Lymphocytes - immunology; cell-mediated immunity; Enzyme-Linked Immunosorbent Assay; Experimental protozoal diseases and models; Female; Fungal and Parasitic Infections; Heligmosomoides polygyrus; histopathology; ileum; immune response; Infectious diseases; Interferon-gamma - blood; interferons; intestines; Intestines - pathology; Leukocyte Reduction Procedures; liver; Liver - pathology; Medical sciences; Mice; Mice, Inbred C57BL; mixed infection; Nematoda; nematode infections; Nematospiroides dubius - immunology; Parasitic diseases; Protozoal diseases; Strongylida Infections - complications; Strongylida Infections - immunology; Survival Analysis; Toxoplasma - immunology; Toxoplasma gondii; toxoplasmosis; Toxoplasmosis - immunology; Toxoplasmosis, Cerebral - immunology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.01236-07

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-γ), 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-γ 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.