Muc5ac: a critical component mediating the rejection of enteric nematodes

Hasnain, Sumaira Z., Evans, Christopher M., Roy, Michelle, Gallagher, Amanda L., Kindrachuk, Kristen N., Barron, Luke, Dickey, Burton F., Wilson, Mark S., Wynn, Thomas A., Grencis, Richard K. and Thornton, David J. (2011) Muc5ac: a critical component mediating the rejection of enteric nematodes. Journal of Experimental Medicine, 208 5: 893-900. doi:10.1084/jem.20102057

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Author Hasnain, Sumaira Z.
Evans, Christopher M.
Roy, Michelle
Gallagher, Amanda L.
Kindrachuk, Kristen N.
Barron, Luke
Dickey, Burton F.
Wilson, Mark S.
Wynn, Thomas A.
Grencis, Richard K.
Thornton, David J.
Title Muc5ac: a critical component mediating the rejection of enteric nematodes
Journal name Journal of Experimental Medicine   Check publisher's open access policy
ISSN 0022-1007
Publication date 2011
Sub-type Article (original research)
DOI 10.1084/jem.20102057
Open Access Status Not yet assessed
Volume 208
Issue 5
Start page 893
End page 900
Total pages 8
Place of publication New York, NY United States
Publisher Rockefeller University Press
Language eng
Formatted abstract
De novo expression of Muc5ac, a mucin not normally expressed in the intestinal tract, is induced in the cecum of mice resistant to Trichuris muris infection. In this study, we investigated the role of Muc5ac, which is detected shortly before worm expulsion and is associated with the production of interleukin-13 (IL-13), in resistance to this nematode. Muc5ac-deficient mice were incapable of expelling T. muris from the intestine and harbored long-term chronic infections, despite developing strong TH2 responses. Muc5ac-deficient mice had elevated levels of IL-13 and, surprisingly, an increase in the TH1 cytokine IFN-γ. Because TH1 inflammation is thought to favor chronic nematode infection, IFN-γ was neutralized in vivo, resulting in an even stronger TH2-type immune response. Nevertheless, despite a more robust TH2 effector response, the Muc5ac-deficient mice remained highly susceptible to chronic T. muris infection. Importantly, human MUC5AC had a direct detrimental effect on nematode vitality. Moreover, the absence of Muc5ac caused a significant delay in the expulsion of two other gut-dwelling nematodes (Trichinella spiralis and Nippostrongylus brasiliensis). Thus, for the first time, we identify a single mucin, Muc5ac, as a direct and critical mediator of resistance during intestinal nematode infection.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Mater Research Institute-UQ (MRI-UQ)
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