Effects of mannan oligosaccharide on immune function and disease resistance in pigs

The 3 studies described below demonstrate the effects of mannan oligosaccharide (MOS) on immune function and disease resistance in pigs. Study 1 evaluated whether MOS in both in vivo and in vitro systems regulates cytokine production by alveolar macrophages (AM??) in response to in vitro microbial challenge models. The lipopolysaccharide (LPS)- stimulated AM?? from MOS-fed pigs produced less tumor necrosis factor-?? (TNF-??) (P < 0.01) and more IL-10 (P = 0.051) than AM?? from the control-fed pigs. Dietary MOS did not affect AM??-produced cytokines induced by polyinosinic:polycytidylic acid (Poly I:C). When applied in vitro, MOS suppressed LPS-induced TNF-?? (P < 0.001), but enhanced LPS-induced IL-10 (P < 0.05). Further, TNF-?? production by AM?? stimulated with LPS (P < 0.05) or Poly I:C (P < 0.001) was suppressed by a mannan-rich fraction (MRF). In order to learn if MOS interacts with LPS receptors, AM?? were cultured with Polymyxin B, an inhibitor of LPS-activated toll-like receptor (TLR) 4. Although Polymyxin B completely inhibited AM??-produced TNF-?? induced by LPS, it did not affect the ability of MOS to regulate cytokine production in the absence of LPS. When added in vitro, both MOS and MRF were also able to regulate constitutive production of TNF-?? in the absence of LPS. Study 2 determined if various levels of dietary MOS affect growth and serum cytokine levels in nursery pigs. No effect of MOS on growth was found. There were no differences in serum levels of TNF-?? and IL-10, although these levels changed over time. Study 3 showed that MOS altered nursery pigs??? immune response to a porcine reproductive and respiratory syndrome virus (PRRSV). Infection of PRRSV reduced pig performance and leukocytes (P < 0.01), but increased serum inflammatory mediators and fever (P < 0.01). Dietary MOS prevented leukopenia at d 3 and 7 postinfection (PI) and tended to improve feed efficiency. In infected pigs, MOS reduced fever at d 7 PI (P < 0.01) and serum TNF-?? at d 14 PI (P = 0.06). The gene expression profile in peripheral blood mononuclear cells and bronchoalveolar lavage fluid cells at d 7 PI was characterized by using microarray and real time RT-PCR. The MOS x PRRSV interaction altered the gene expression in the above leukocytes (P < 0.05). In peripheral blood mononuclear cells, MOS increased the gene expression of pattern recognition receptors, cytokines, and intracellular signaling molecules in uninfected pigs, but reduced the gene expression of TLR4 and various types of key cytokines and chemokines in infected pigs (P < 0.05). In bronchoalveolar lavage fluid cells, MOS may promote a cytotoxic T cell immune response by enhancing MHCI mRNA expression, but reduce the expression of complement system-associated molecules and 2???,5???-oligoadenylate synthetase-1. The downregulation of inflammatory responses regulated by MOS at d 7 PI was associated with several important canonical pathways such as triggering receptor expressed on myeloid cells-1 signaling, hypoxia signaling, IL-4 signaling, macropinocytosis signaling, and perhaps the alternative activation of macrophages. In summary, MOS is a potent immunomodulator in both in vitro and in vivo systems. Dietary inclusion of MOS in diets for pigs may bring benefits by boosting and maintaining the host???s disease resistance while preventing over-stimulation of the immune system