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-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.