Specificity and effector functions of human RSV-specific IgG from bovine milk

Background Respiratory syncytial virus (RSV) infection is the second most important cause of death in the first year of life, and early RSV infections are associated with the development of asthma. Breastfeeding and serum IgG have been shown to protect against RSV infection. Yet, many infants depend on bovine milk-based nutrition, which at present lacks intact immunoglobulins. Objective To investigate whether IgG purified from bovine milk (bIgG) can modulate immune responses against human RSV. Methods ELISAs were performed to analyse binding of bIgG to human respiratory pathogens. bIgG or hRSV was coated to plates to assess dose-dependent binding of bIgG to human Fc¿ receptors (Fc¿R) or bIgG-mediated binding of myeloid cells to hRSV respectively. S. Epidermidis and RSV were used to test bIgG-mediated binding and internalisation of pathogens by myeloid cells. Finally, the ability of bIgG to neutralise infection of HEp2 cells by hRSV was evaluated. Results bIgG recognised human RSV, influenza haemagglutinin and Haemophilus influenza. bIgG bound to Fc¿RII on neutrophils, monocytes and macrophages, but not to Fc¿RI and Fc¿RIII, and could bind simultaneously to hRSV and human Fc¿RII on neutrophils. In addition, human neutrophils and dendritic cells internalised pathogens that were opsonised with bIgG. Finally, bIgG could prevent infection of HEp2 cells by hRSV. Conclusions The data presented here show that bIgG binds to hRSV and other human respiratory pathogens and induces effector functions through binding to human Fc¿RII on phagocytes. Thus bovine IgG may contribute to immune protection against RSV

Vectorial secretion of interleukin-8 mediates autocrine signalling in intestinal epithelial cells via apically located CXCR1

BackgroundIn the intestinal mucosa, several adaptations of TLR signalling have evolved to avoid chronic inflammatory responses to the presence of commensal microbes. Here we investigated whether polarized monolayers of intestinal epithelial cells might regulate inflammatory responses by secreting IL-8 in a vectorial fashion (i.e. apical versus basolateral) depending on the location of the TLR stimulus.ResultsIn the Caco-2 BBE model of polarized villus-like epithelium, apical stimulation with TLR2 and TLR5 ligands resulted in the apical secretion of IL-8. The CXCR1 receptor for IL-8 was expressed only on the apical membrane of Caco-2 BBE cells and differentiated epithelial cells in the human small intestine and colon. Transcriptome analyses revealed that Caco-2 BBE cells respond to stimulation with IL-8 supporting the hypothesis that IL-8 induces G protein-coupled receptor signalling.ConclusionsThese results show that IL-8 induces autocrine signalling via an apical CXCR1 in Caco-2 BBE intestinal epithelial cells and that this receptor is also expressed on the apical surface of differentiated human intestinal epithelial cells in vivo, suggesting an autocrine function for IL-8 secreted in the lumen

A Consideration of Biomarkers to be Used for Evaluation of Inflammation in Human Nutritional Studies

To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammatio

The effects of milk and colostrum on allergy and infection: mechanisms and implications

Children that grow up on farms have fewer allergies than children growing up in city environments. This protection against the development of allergy is associated with the consumption of raw farm milk. Heated farm milk does not have this effect, indicating that (non-denatured) milk proteins are responsible for this effect. The consumption of normal bovine colostrum protects immunocompromised people against infections. Bovine milk proteins have immunological effects on human cells. Currently, raw milk is not commercially available and cannot be used for controlled intervention studies because of the potential presence of pathogenic microorganisms. Alternative milk-processing technologies are needed to preserve immune active milk proteins that can improve immunity in children

Nutrition and allergic diseases

The development of IgE-mediated allergic diseases is influenced by many factors, including genetic and environmental factors such as pollution and farming, but also by nutrition. In the last decade, substantial progress has been made in our understanding of the impact that nutrition can have on allergic diseases. Many studies have addressed the effect of breastfeeding, pre-, pro- and synbiotics, vitamins and minerals, fiber, fruit and vegetables, cow’s milk, and n-3 fatty acids, on the development of allergies. In addition, nutrition can also have indirect effects on allergic sensitization. This includes the diet of pregnant and breastfeeding women, which influences intrauterine development, as well as breastmilk composition. These include the diet of pregnant and breastfeeding women that influences intrauterine development as well as breastmilk composition, effects of food processing that may enhance allergenicity of foods, and effects via modulation of the intestinal microbiota and their metabolites. This editorial review provides a brief overview of recent developments related to nutrition and the development and management of allergic diseases

Cow's Milk and Allergy

The purpose of this Special Issue “Cow’s Milk and Allergy” is to provide an overview of the association of cow’s milk with allergy. This topic has two quite different faces. On the one hand, we are all aware of the importance of cow’s milk allergy in early life. What is less known is that the consumption of raw, unprocessed milk is associated with a lower incidence of asthma and rhinitis. This Special Issue takes a closer look at all of these aspects of cow’s milk and allergy and focus on the following questions

Hypoallergenic infant formula and methods for preparing the same

The invention relates to the field of infant nutritional formulations, in particular to methods for providing a hypoallergenic nutritional composition based on cow's milk protein for infants who are at risk of developing cow's milk allergy (CMA). The method comprises the steps of: (i) providing a partial hydrolysate of the milk protein(s), obtained by subjecting a starting composition comprising one or more bovine milk protein(s) in an aqueous medium to an enzymatic treatment, (ii) clearing the partial hydrolysate from one or more components capable of RAGE- binding and/or having a basophil degranulation inducing capacity; (iii) optionally concentrating the cleared partial hydrolysate; and (iv) formulating the (concentrated) cleared partial hydrolysate into a nutritional composition for infants who are at risk of developing CMA

Hypoallergenic infant formula and methods for preparing the same

The invention relates to the field of infant nutritional formulations, in particular to methods for providing a hypoallergenic nutritional composition based on cow's milk protein for infants who are at risk of developing cow's milk allergy (CMA). The method comprises the steps of: (i) providing a partial hydrolysate of the milk protein(s), obtained by subjecting a starting composition comprising one or more bovine milk protein(s) in an aqueous medium to an enzymatic treatment, (ii) clearing the partial hydrolysate from one or more components capable of RAGE- binding and/or having a basophil degranulation inducing capacity; (iii) optionally concentrating the cleared partial hydrolysate; and (iv) formulating the (concentrated) cleared partial hydrolysate into a nutritional composition for infants who are at risk of developing CMA