Mucin gene deficiency in mice impairs host resistance to an enteric parasitic infection.
OBJECTIVE
Hyperplasia of mucin-secreting intestinal goblet cells accompanies a number of enteric infections, including infections by nematode parasites. Nevertheless, the precise role of mucins in host defense in nematode infection is not known. We investigated the role of the mucin (Muc2) in worm expulsion and host immunity in a model of nematode infection.


METHODS
Resistant (BALB/c, C57BL/6), susceptible (AKR), and Muc2-deficient mouse strains were infected with the nematode, Trichuris muris, and worm expulsion, energy status of the whipworms, changes in mucus/mucins, and inflammatory and immune responses were investigated after infection.


RESULTS
The increase in Muc2 production, observed exclusively in resistant mice, correlated with worm expulsion. Moreover, expulsion of the worms from the intestine was significantly delayed in the Muc2-deficient mice. Although a marked impairment in the development of periodic acid Schiff (PAS)-stained intestinal goblet cells was observed in Muc2-deficient mice, as infection progressed a significant increase in the number of PAS-positive goblet cells was observed in these mice. Surprisingly, an increase in Muc5ac, a mucin normally expressed in the airways and stomach, was observed after infection of only the resistant animals. Overall, the mucus barrier in the resistant mice was less permeable than that of susceptible mice. Furthermore, the worms isolated from the resistant mice had a lower energy status.


CONCLUSIONS
Mucins are an important component of innate defense in enteric infection; this is the first demonstration of the important functional contribution of mucins to host protection from nematode infection.
Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
Sumaira Z
SZ
Hasnain
Huaqing
H
Wang
Jean-Eric
JE
Ghia
Nihal
N
Haq
Yikang
Y
Deng
Anna
A
Velcich
Richard K
RK
Grencis
David J
DJ
Thornton
Waliul I
WI
Khan
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism; D020397:Goblet Cells / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007411:Intestinal Diseases, Parasitic / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D055271:Mucin 5AC / Q000378:metabolism; D055262:Mucin-2 / Q000172:deficiency* / Q000235:genetics; D010539:Permeability; D013045:Species Specificity; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D013997:Time Factors; D014257:Trichuriasis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology / Q000517:prevention & control; D014258:Trichuris / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*
C524626:Muc2 protein, mouse; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D055262:Mucin-2; D000255:Adenosine Triphosphate