Characterising the mucosal and systemic immune responses to experimental human hookworm infection

Gaze, Soraya, McSorley, Henry J., Daveson, James, Jones, Di, Bethony, Jeffrey M., Oliveira, Luciana M., Speare, Richard, McCarthy, James S., Engwerda, Christian R., Croese, John, and Loukas, Alex (2012) Characterising the mucosal and systemic immune responses to experimental human hookworm infection. PLoS Pathogens, 8 (2). e1002520. pp. 1-11.

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Abstract

The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13) and regulatory (IL-10 and TGF-β) response, with some evidence of a Th1 (IFN-γ and IL-2) response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17) response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases.

Item ID: 22208
Item Type: Article (Research - C1)
ISSN: 1553-7374
Funders: National Health and Medical Research Council (NHMRC), Broad Foundation
Date Deposited: 28 Jun 2012 15:48
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 50%
SEO Codes: 92 HEALTH > 9299 Other Health > 929999 Health not elsewhere classified @ 100%
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