Immunological relationships during primary infection with<i>Heligmosomoides polygyrus</i>: Th2 cytokines and primary response phenotype

Wahid, Faisal; Behnke, Jerzy M.; Grencis, Richard K.; Else, Kathryn J.; Ben-Smith, A.W.

doi:10.1017/s0031182000076022

Cited by 59 publications

(53 citation statements)

References 31 publications

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“…Measurement of cytokine production by T cells during intestinal nematode infection after stimulation in vitro or by analysis of cytokine mRNA expression showed a predominance of Th2-type responses. This response has been shown for N. brasiliensis (Finkelman et al 1997;Lawrence et al 1996), T. spiralis , H. polygyrus (Wahid et al 1994;Behnke et al 1993) and T. muris Else et al 1992).…”

Section: C On T Rol Of I M M U N I T Y By T H E L Pe R C E L L Su Bmentioning

confidence: 61%

Th2–mediated host protective immunity to intestinal nematode infections

Grencis

1997

Phil. Trans. R. Soc. Lond. B

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124

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Despite many years of study, relatively little is known about the effector mechanisms that operate against intestine–dwelling nematodes. Most of the current understanding comes from studies of laboratory model systems in rodents. It is clear that when an intestinal helminth infection takes place the immune system generates a strong Th2–mediated response, which regulates a variety of responses characteristic of helminth infections such as eosinophilia, intestinal mastocytosis and elevated IgE production. The ability to modulate the host's immune response in vivo with cytokine–specific monoclonal antibodies and recombinant cytokines, together with the use of animals with disruption of key genes involved in the immune response, have provided powerful tools with which to dissect the potential effector mechanisms operating. In the absence of a T–cell compartment the host is unable to expel the parasite. If a Th1–dominated response is generated, protective immunity is almost universally compromised. Thus, it would appear that some aspect of Th2–mediated response controls effector mechanisms. Although it is clear that for some infections the mast cell appears to be involved in protection, probably through the generation of a non–specific inflammatory response, how these cells become activated remains unclear. Data from infections in transgenic animals suggest that activation is not through the high–affinity receptor for IgE. Such studies also call into doubt the importance of conventional interactions between effector leucocytes and antibody. There is little evidence to support a protective role for eosinophilia in any system. New data also imply that , although interleukin 4 (IL–4) is generally important (and can exert effects independent of an adaptive immune response), it is not always sufficient to mediate protection; other Th2 cytokines (e.g. IL–13) may warrant closer investigation. It is apparent that a number of potential Th2–controlled effector mechanisms (some of which may be particularly important at mucosal surfaces) remain to be explored. Overall, it is likely that worm expulsion is the result of a combination of multiple mechanisms, some of which are more critical to some species of parasite than to others.

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Section: C On T Rol Of I M M U N I T Y By T H E L Pe R C E L L Su Bmentioning

confidence: 61%

Th2–mediated host protective immunity to intestinal nematode infections

Grencis

1997

Phil. Trans. R. Soc. Lond. B

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124

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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).…”

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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“…This suggests that hosts with a higher potential for productive functions may allocate more nutrients to such functions when nutrients are scarce, at the expense of functions involved with limiting parasitism, including anti-helminth immune responses (Wahid et al 1994). Here, we hypothesize that this penalty on resilience in ROH mice will decrease with lower infection levels and that ROL mice will tolerate higher infection levels.…”

Section: Introductionmentioning

confidence: 91%

Interactive effects of protein nutrition, genetic growth potential andHeligmosomoides bakeriinfection pressure on resilience and resistance in mice

Coltherd

Babayan

Bünger³

et al. 2011

Parasitology

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SUMMARYThe ability of animals to cope with an increasing parasite load, in terms of resilience and resistance, may be affected by both nutrient supply and demand. Here, we hypothesized that host nutrition and growth potential interact and influence the ability of mice to cope with different parasite doses. Mice selected for high (ROH) or low (ROL) body weight were fed a low (40 g/kg; LP) or high (230 g/kg; HP) protein diet and infected with 0, 50, 100, 150, 200 or 250 L3infectiveHeligmosomoides bakerilarvae. ROH-LP mice grew less at doses of 150 L3and above, whilst growth of ROH-HP and of ROL mice was not affected by infection pressure. Total worm burdens reached a plateau at doses of 150L3, whilst ROH mice excreted fewer worm eggs than ROL mice. Serum antibodies increased with infection dose and ROH mice were found to have higher parasite-specific IgG1 titres than ROL mice. In contrast, ROL had higher total IgE titres than ROH mice, only on HP diets. The interaction between host nutrition and growth potential appears to differentially affect resilience and resistance in mice. However, the results support the view that parasitism penalises performance in animals selected for higher growth.

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Immunological relationships during primary infection withHeligmosomoides polygyrus: Th2 cytokines and primary response phenotype

Cited by 59 publications

References 31 publications

Th2–mediated host protective immunity to intestinal nematode infections

Th2–mediated host protective immunity to intestinal nematode infections

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

Interactive effects of protein nutrition, genetic growth potential andHeligmosomoides bakeriinfection pressure on resilience and resistance in mice

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Immunological relationships during primary infection withHeligmosomoides polygyrus: Th2 cytokines and primary response phenotype

Cited by 59 publications

References 31 publications

Th2–mediated host protective immunity to intestinal nematode infections

Th2–mediated host protective immunity to intestinal nematode infections

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

Interactive effects of protein nutrition, genetic growth potential andHeligmosomoides bakeriinfection pressure on resilience and resistance in mice

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