Delayed bacterial colonization of the gut alters the host immune response to oral sensitization against cow's milk proteins.

Scope: Cow's milk allergy is the most prevalent food allergy in infants whose immune system development is critically stimulated during postnatal gut colonization by commensal bacteria. Allergenic potential of cow's milk β-lactoglobulin (BLG) and caseins (CAS) was investigated in germ-free (GF) BALB/c mice and in GF mice conventionalized (CVd) at 6 weeks of age.

Methods And Results: Oral sensitization to cow's milk in the presence of cholera toxin led to higher BLG-specific IgE, IgG1, and IgG2a responses in GF mice than in conventional (CV) mice.

Early postprandial low-grade inflammation after high-fat meal in healthy rats: possible involvement of visceral adipose tissue.

In the postprandial period, low-grade inflammation may contribute to vascular endothelial dysfunction, a hallmark of atherogenesis. Little is known about the involvement of the adipose tissue in the initiation of the postprandial inflammatory response such as obtained after a high-saturated fat meal (HFM). In the present study, we first studied the time course of appearance of systemic inflammation after a HFM in healthy rats, and then we investigated whether a HFM activates the inflammatory signaling in the visceral adipose tissue, with a focus on the key component, nuclear factor-kappaB (NF-kappaB).

Uptake of ingested bovine lactoferrin and its accumulation in adult mouse tissues.

Lactoferrin is a glycoprotein with antimicrobial and immunoregulatory properties, which is found in milk, other external secretions, and in the secondary granules of neutrophils. The present study examined the time course of uptake and the pattern of tissue accumulation of bovine lactoferrin (bLf) following intragastric intubation of a single dose to adult naïve mice or to mice daily fed bLf for 4 weeks. Following ingestion, bLf was transferred from the intestine into peripheral blood in a form with intact molecular weight (80 kDa) and localized within 10 to 20 min after oral administration in the liver, kidneys, gall bladder, spleen, and brain of both groups of mice.

Th1 and Th2 cells are required for both eosinophil- and neutrophil-associated airway inflammatory responses in mice.

Most current animal models focus on eosinophil-mediated asthma, despite compelling evidence that a neutrophil-mediated disease occurs in some asthma patients. Using intranasal challenge of mice sensitized either orally or nasally with whole peanut protein extract in the presence of cholera toxin, we developed mouse models of eosinophil- and neutrophil-mediated asthma, respectively. In this study, mice deficient in Th1 (IL-12 and IFN-gamma) or Th2 (IL-4 and IL-13) pathways were used to characterize the role played by Th1 and Th2 cytokines during the initial priming phase in the two models.

Regulation of physiological and pathological Th1 and Th2 responses by lactoferrin.

In recent years, Lf has gained increasing interest as a result of its protective effects against a variety of diseases. While iron binding and interactions with mammalian receptors and microbial components are the best described mechanisms of action, recent studies have provided evidence that Lf properties may be related to immunoregulatory effects on Th1/Th2 cell activities. In vitro and in vivo experiments show that Lf is able to stimulate the differentiation of T cells from their immature precursors through the induction of the CD4 antigen.

Bacillus anthracis edema toxin acts as an adjuvant for mucosal immune responses to nasally administered vaccine antigens.

Anthrax edema toxin (EdTx) is an AB-type toxin that binds to anthrax toxin receptors on target cells via the binding subunit, protective Ag (PA). Edema factor, the enzymatic A subunit of EdTx, is an adenylate cyclase. We found that nasal delivery of EdTx enhanced systemic immunity to nasally coadministered OVA and resulted in high OVA-specific plasma IgA and IgG (mainly IgG1 and IgG2b).

Oral and nasal sensitization promote distinct immune responses and lung reactivity in a mouse model of peanut allergy.

Despite structural and functional differences between the initial sites of contact with allergens in the gastrointestinal and nasal tracts, few animal models have examined the influence of the mucosal routes of sensitization on host reactivity to food or environmental antigens. We compared the oral and nasal routes of peanut sensitization for the development of a mouse model of allergy. Mice were sensitized by administration of peanut proteins in the presence of cholera toxin as adjuvant.

Therapeutic manipulation of the immune system: enhancement of innate and adaptive mucosal immunity.

The mucosal immune system has evolved alongside, but separate, from the general systemic immune system. As a major consequence of this dichotomy, only immune responses initiated in mucosal inductive sites can result in effective immunity in mucosal tissues themselves. Oral tolerance, as usually assessed as orally-induced systemic unresponsiveness, contributes to mucosal homoeostasis by preventing unwanted immune reactions to food or environmental antigens.

Effective mucosal immunity to anthrax: neutralizing antibodies and Th cell responses following nasal immunization with protective antigen.

Mucosal, but not parenteral, immunization induces immune responses in both systemic and secretory immune compartments. Thus, despite the reports that Abs to the protective Ag of anthrax (PA) have both anti-toxin and anti-spore activities, a vaccine administered parenterally, such as the aluminum-adsorbed anthrax vaccine, will most likely not induce the needed mucosal immunity to efficiently protect the initial site of infection with inhaled anthrax spores. We therefore took a nasal anthrax vaccine approach to attempt to induce protective immunity both at mucosal surfaces and in the peripheral immune compartment.