<i>Heligmosomoides polygyrus</i>Promotes Regulatory T-Cell Cytokine Production in the Murine Normal Distal Intestine

Setiawan, Tommy; Metwali, Ahmed; Blum, Arthur M.; Ince, M. Nedim; Urban, Joseph F.; Elliott, David E.; Weinstock, Joel V.

doi:10.1128/iai.00358-07

Cited by 112 publications

(120 citation statements)

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“…After two larval molts in the submucosa, the male and female adult worms emerge into the lumen of the intestine and mate, and eggs are excreted in the feces (44). Infection with H. polygyrus, although completely enteric, results in systemic dissemination and induction of Th2 cytokine responses (35,38,43,44). Such Th2 cytokine responses have been shown to block type 1 cytokine responses (1,24) and to induce regulatory T cells (46).…”

Section: Cd8mentioning

confidence: 99%

Coinfection withHeligmosomoides polygyrusFails To Establish CD8⁺T-Cell Immunity againstToxoplasma gondii

et al. 2008

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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.

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Section: Cd8mentioning

confidence: 99%

Coinfection withHeligmosomoides polygyrusFails To Establish CD8⁺T-Cell Immunity againstToxoplasma gondii

et al. 2008

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“…In animal models, the beneficial effects of nematode infections on inflammatory disorders were associated with the presence of Treg populations [6,11,12]. However, it is not yet clear whether such Treg suppress anti-parasite immune reactivity and thus contribute to survival and well-being of the worms, or whether they predominantly dampen immunopathology.…”

Section: Introductionmentioning

confidence: 99%

“…It has been demonstrated that nematode infections may prevent and control undesired immune reactions [6][7][8][9][10][11][12]30]. Several studies showed that the beneficial effects of the infections could be mimicked by transfer of Treg derived from nematode-infected donors to naïve recipients rendering them refractory to the inflammatory disorders such as asthma and colitis [6,8,11,12]. These data indicate that circuits of Treg action during nematode infection may also modulate unrelated bystander immune reactions and supports the view of Treg as important immunoregulators that can be modulated by parasites.…”

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confidence: 99%

Establishment of nematode infection despite increased Th2 responses and immunopathology after selective depletion of Foxp3⁺ cells

et al. 2009

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Here, we show that Treg limit intestinal pathology during nematode infection and that they control the onset and magnitude of the anti-parasitic Th Th2 response. Using mice expressing the diptheria toxin receptor under the control of the foxp3 locus, we removed Foxp3 1 Treg during the early phase of infection with Heligmosomoides polygyrus bakeri. Depletion of Treg in infected animals did not affect adult worm burden, but led to increased pathology at the site of infection. Infected, depleted mice displayed higher frequencies of activated CD4 1 T cells and increased levels of the Th2 cytokines IL-4 and IL-13. The stronger parasite-specific Th2 response was accompanied by higher levels of IL-10. Only a moderate change in Th1 (IFN-c) reactivity was detected in worm-infected, Treg-depleted mice. Furthermore, we detected an accelerated onset of parasite-specific Th2 and IL-10 responses in the transient absence of Foxp3 1 Treg. However, adult worm burdens were not affected by the increased Th2-reactivity in Treg-depleted mice. Hence, our data show that Treg restrict the onset and strength of Th2 responses during intestinal worm infection, while increasing primary Th2 responses does not necessarily lead to killing of larvae or accelerated expulsion of adult worms.Key words: Foxp3 . Nematode . Pathology . Th2 response . Treg IntroductionParasitic worms are the most potent inducers of highly polarized Th cell type 2 (Th2) responses. Helminth infections tend to be long lasting and are often associated with insufficient immunity to re-infection [1,2]. Chronic infections favor immunosuppression, the so-called modulated Th2-response, associated with poor parasite-specific reactivity alongside with the strong production of anti-inflammatory cytokines, such as . This helminth-induced immunosuppression may spill over to bystander antigens [3], downmodulate reactivity against other pathogens [4] and impair vaccination efficacy [5]. However, such effects can be beneficial by downregulating inflammatory reactions to allergens and inflammatory disorders of the intestinal tract. Studies in animal models showed that helminths can suppress airway hyperreactivity and colitis [6][7][8] and nematodes have been used to efficiently treat human inflammatory bowel disease in clinical trials [9,10]. 3066In animal models, the beneficial effects of nematode infections on inflammatory disorders were associated with the presence of Treg populations [6,11,12]. However, it is not yet clear whether such Treg suppress anti-parasite immune reactivity and thus contribute to survival and well-being of the worms, or whether they predominantly dampen immunopathology. Several studies investigated the role of Treg in infections with helminths or other parasites and yielded in diverging conclusions (reviewed in [1] and [13]). There is evidence that certain parasites depend on Treg action for their persistence [14][15][16][17]. Other species profit more indirectly from Treg circuits, which control infectioninduced pathology [18][19][20].In a previous study ...

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“…For this reason, we have begun to work with an experimental model of co-infection with T. gondii and Heligmosomoides polygyrus, which has been shown as valid model for studying parasites that evoke polar Th-1 and Th-2 in mice. H. polygyrus is a gastrointestinal worm, a natural parasite to mice, which evokes a polarized Th2 response in the host and blocks the type 1 immune response [39,40]. It has been shown that a previous infection with the helminth can inhibit the development of CD8 T-cell immune response against T. gondii, thus compromising long-term protection against a protozoan parasite [41], which illustrates the adequacy of the model for studying the interaction between helminthic and T. gondii infections.…”

Section: Ocular Toxoplasmosis In Association With Other Infectious DImentioning

confidence: 99%

Immunological and Immunogenetic Parameters on the Diversity of Ocular Toxoplasmosis: Evidence to Support Morphological Criteria to Classify Retinal/Retinochoroidal Scar Lesions in Epidemiologic Surveys

Bahia-Oliveira¹,

Rangel²,

Boechat³

et al. 2012

Toxoplasmosis - Recent Advances

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Heligmosomoides polygyrusPromotes Regulatory T-Cell Cytokine Production in the Murine Normal Distal Intestine

Cited by 112 publications

References 31 publications

Coinfection withHeligmosomoides polygyrusFails To Establish CD8⁺T-Cell Immunity againstToxoplasma gondii

Coinfection withHeligmosomoides polygyrusFails To Establish CD8⁺T-Cell Immunity againstToxoplasma gondii

Establishment of nematode infection despite increased Th2 responses and immunopathology after selective depletion of Foxp3⁺ cells

Immunological and Immunogenetic Parameters on the Diversity of Ocular Toxoplasmosis: Evidence to Support Morphological Criteria to Classify Retinal/Retinochoroidal Scar Lesions in Epidemiologic Surveys

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Heligmosomoides polygyrusPromotes Regulatory T-Cell Cytokine Production in the Murine Normal Distal Intestine

Cited by 112 publications

References 31 publications

Coinfection withHeligmosomoides polygyrusFails To Establish CD8+T-Cell Immunity againstToxoplasma gondii

Coinfection withHeligmosomoides polygyrusFails To Establish CD8+T-Cell Immunity againstToxoplasma gondii

Establishment of nematode infection despite increased Th2 responses and immunopathology after selective depletion of Foxp3+ cells

Immunological and Immunogenetic Parameters on the Diversity of Ocular Toxoplasmosis: Evidence to Support Morphological Criteria to Classify Retinal/Retinochoroidal Scar Lesions in Epidemiologic Surveys

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Coinfection withHeligmosomoides polygyrusFails To Establish CD8⁺T-Cell Immunity againstToxoplasma gondii

Coinfection withHeligmosomoides polygyrusFails To Establish CD8⁺T-Cell Immunity againstToxoplasma gondii

Establishment of nematode infection despite increased Th2 responses and immunopathology after selective depletion of Foxp3⁺ cells