Coinfection with Heligmosomoides polygyrus fails to establish CD8 + T-cell immunity against Toxoplasma gondii

Imtiaz A. Khan, Rubeena Hakak, Karen Eberle, Peter Sayles, Louis M. Weiss, Joseph F. Urban

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1305-1313
Number of pages9
JournalInfection and Immunity
Volume76
Issue number3
DOIs
StatePublished - Mar 2008

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Nematospiroides dubius
Toxoplasma
Coinfection
Immunity
T-Lymphocytes
Toxoplasmosis
Infection
Parasites
Cytokines
Encephalitis
Interferons
Interferon-gamma

ASJC Scopus subject areas

  • Immunology

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Coinfection with Heligmosomoides polygyrus fails to establish CD8 + T-cell immunity against Toxoplasma gondii. / Khan, Imtiaz A.; Hakak, Rubeena; Eberle, Karen; Sayles, Peter; Weiss, Louis M.; Urban, Joseph F.

In: Infection and Immunity, Vol. 76, No. 3, 03.2008, p. 1305-1313.

Research output: Contribution to journalArticle

Khan, Imtiaz A. ; Hakak, Rubeena ; Eberle, Karen ; Sayles, Peter ; Weiss, Louis M. ; Urban, Joseph F. / Coinfection with Heligmosomoides polygyrus fails to establish CD8 + T-cell immunity against Toxoplasma gondii. In: Infection and Immunity. 2008 ; Vol. 76, No. 3. pp. 1305-1313.
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