Effect of Heat-Killed Escherichia coli, Lipopolysaccharide, and Muramyl Dipeptide Treatments on the Immune Response Phenotype and Allergy in Neonatal Pigs Sensitized to the Egg White Protein Ovomucoid

Abstract

Predisposition to food allergies may reflect a type 2 immune response (IR) bias in neonates due to the intrauterine environment required to maintain pregnancy. The hygiene hypothesis states that lack of early environmental stimulus leading to inappropriate development and bias in IR may also contribute. Here, the ability of heat-killed Escherichia coli, lipopolysaccharide (LPS), or muramyl dipeptide (MDP) to alter IR bias and subsequent allergic response in neonatal pigs was investigated. Three groups of three litters of pigs (12 pigs/litter) were given intramuscular injections of E. coli, LPS, MDP, or phosphate-buffered saline (PBS) (control) and subsequently sensitized to the egg white allergen ovomucoid using an established protocol. To evaluate change in IR bias, immunoglobulin isotype-associated antibody activity (AbA), concentrations of type 1 and 2 and proinflammatory cytokines released from mitogen-stimulated blood mononuclear cells, and the percentage of T-regulatory cells (T-regs) in blood were measured. Clinical signs of allergy were assessed after oral challenge with egg white. The greatest effect on IR bias was observed in MDP-treated pigs, which had a type 2-biased phenotype by isotype-specific AbA, cytokine production, and a low proportion of T-regs. LPS-treated pigs had decreased type 1- and type 2-associated AbA. E. coli-treated pigs displayed increased response to Ovm as AbA and had more balanced cytokine profiles, as well as the highest proportion of T-regs. Accordingly, pigs treated with MDP were more susceptible to allergy than PBS controls, while pigs treated with LPS were less susceptible. Treatment with E. coli did not significantly alter the frequency of clinical signs.