title: Coinfection with Heligmosomoides polygyrus fails to establish CD8+ T-cell immunity against Toxoplasma gondii.
abstract: 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-), 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- 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.
authors.affiliation: Department of Microbiology and Tropical Medicine and Immunology, George Washington University, Washington, DC 20037, USA. mtmixk@gwumc.edu
authors.forename: Imtiaz A
authors.initials: IA
authors.lastname: Khan
authors.forename: Rubeena
authors.initials: R
authors.lastname: Hakak
authors.forename: Karen
authors.initials: K
authors.lastname: Eberle
authors.forename: Peter
authors.initials: P
authors.lastname: Sayles
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiss
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Urban
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D007422:Intestines / Q000473:pathology; D047589:Leukocyte Reduction Procedures; D008099:Liver / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009351:Nematospiroides dubius / Q000276:immunology*; D017206:Strongylida Infections / Q000150:complications* / Q000276:immunology*; D016019:Survival Analysis; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology*; D016781:Toxoplasmosis, Cerebral / Q000276:immunology
chemical_list: D007371:Interferon-gamma