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Immunomodulating mechanism of oral ß-glucans in pigs could be
hampered by the epithelial mucosal barrier
Eric Cox1, Kim Baert1, Bruno Goddeeris1,2, Bert Devriendt1
1 UGent, 2 KULeuven, Belgium.
The prophylactic use of antibiotics is prohibited in Europe since January 2006.
Therefore, alternatives are searched for in order to prevent infection on
problem farms. Certain ß-glucans, polymers of D-glucose, have the capacity
to activate the innate immune system. In a number of experiments we aimed
to determine if they could increase the resistance against infections with
enterotoxigenic E. coli (ETEC), an important cause of economical losses in
newly weaned piglets and we wanted to understand their mode of action.
Material and methods
Several experiments were performed. In a first experiments four groups of
pigs, either receiving one of three different ß-glucans or no glucans were
challenge infected with F4+ ETEC. In a second experiment, one ß-glucan
preparation was given to 1-week-old gnotobiotic pigs during 35 days,
whereafter these piglets were orally immunized with F4 fimbriae in order to
see an adjuvant effect of the glucans. In a third experimental set up, the effect
of seven different ß-glucans on lymphocyte proliferation, reactive oxygen
species (ROS) production by neutrophils and monocytes and cytokine
production was analyzed. In a fourth experiment, the role of the ß-glucan
receptors dectin-1 and the complement-receptor 3 (CR3) in activation of
monocytes and neutrophils by ß-glucans was examined.
Results
The challenge study in conventionally bred, weaned piglets showed that ßglucans can protect against an ETEC infection. Macrogard from S. cerevisiae
and scleroglucan significantly reduced faecal excretion of F4+ ETEC.
No effect of ß-glucans was seen on an oral F4 immunization in gnotobiotic
pigs, suggesting that the glucans did not exert their protective effect by
modulating the humoral mucosal immune response.
Incubating different leukocytes with different ß-glucans showed that these
glucans exerted different effects on the leukocytes. Macrogard induced
production of reactive oxygen species (ROS) by monocytes and neutrophils,
while this was not the case for scleroglucan. The latter enhanced cytokine
production, similar to the induction of cytokines by macrogard. This suggest
that cytokine production rather than ROS production might be important for
protection.
The fourth experiment demonstrated that the complement-receptor 3 (CR3)
plays a cardinal role in ß-glucan receptor recognition and signaling by porcine
neutrophils, while CR3 and dectin-1 were important for activation of
macrophages, similar to what has been seen in man, but not in mice.
Conclusion
Protection of pigs against F4+ ETEC infection is ß-glucan dependent. One of
the protective ß-glucans is macrogard. This ß-glucan does not exert its effect
via an adjuvant effect on antibody production. It activates innate immunity via
the CR3 in neutrophils and via the CR3 and dectin-1 in macrophages. Most
likely crossing the intestinal mucosal barrier is crucial for ß-glucans to exert
their effect on an ETEC infection