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Intestinal helminths protect in a murine model of asthma
Journal article   Peer reviewed

Intestinal helminths protect in a murine model of asthma

Kunihiko Kitagaki, Thomas R Businga, Doina Racila, David E Elliott, Joel V Weinstock and Joel N Kline
The Journal of immunology (1950), Vol.177(3), pp.1628-1635
08/01/2006
DOI: 10.4049/jimmunol.177.3.1628
PMID: 16849471

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Abstract

Underdeveloped nations are relatively protected from the worldwide asthma epidemic; the hygiene hypothesis suggests this is due to suppression of Th2-mediated inflammation by increased exposure to pathogens and their products. Although microbial exposures can promote Th2-suppressing Th1 responses, even Th2-skewing infections, such as helminths, appear to suppress atopy, suggesting an alternate explanation for these observations. To investigate whether induction of regulatory responses by helminths may counter allergic inflammation, we examined the effects of helminth infection in a murine model of atopic asthma. We chose Heligosomoides polygyrus, a gastrointestinal nematode, as the experimental helminth; this worm does not enter the lung in its life cycle. We found that H. polygyrus infection suppressed allergen-induced airway eosinophilia, bronchial hyperreactivity, and in vitro allergen-recall Th2 responses in an IL-10-dependent manner; total and OVA-specific IgE, however, were increased by worm infection. Finally, helminth-infected mice were protected against eosinophilic inflammation induced by adoptive transfer of OVA-stimulated CD4(+) cells, and transfer of cells from helminth-infected/OVA-exposed mice suppressed OVA-induced eosinophilic inflammation, suggesting a role for regulatory cells. Increased CD4(+)CD25(+)Foxp3(+) cells were found in thoracic lymph nodes of helminth-infected/OVA-exposed mice. Helminthic colonization appears to protect against asthma and atopic disorders; the regulatory cytokine, IL-10, may be a critical player.
Asthma - parasitology Spleen - immunology Asthma - prevention & control Immunoglobulin E - biosynthesis Th2 Cells - immunology Interleukin-10 - physiology Nematospiroides dubius - immunology Eosinophilia - pathology Th2 Cells - parasitology Immunoglobulin G - biosynthesis Strongylida Infections - immunology Gastrointestinal Diseases - pathology Female Gastrointestinal Diseases - immunology Disease Models, Animal Gastrointestinal Diseases - parasitology Interleukin-10 - deficiency Eosinophilia - parasitology Cells, Cultured Nematospiroides dubius - growth & development Spleen - cytology Th2 Cells - metabolism Mice, Knockout Strongylida Infections - pathology Spleen - parasitology Animals Spleen - metabolism Interleukin-10 - genetics Eosinophilia - prevention & control Mice Mice, Inbred BALB C Cytokines - antagonists & inhibitors Asthma - pathology Cytokines - biosynthesis

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