دانلود مقاله شیر گاو و عملکرد ایمن سازی در دستگاه تنفسی
Abstract
Introduction
Homology Between Cow’s Milk and Breast Milk
Epidemiological Evidence for the Immune Modulatory Role of Cow’s Milk on Respiratory Health
Passage Through the Gastrointestinal Tract
Binding of Bovine IgG to Respiratory Pathogens
The First Host Barrier: The Epithelium
Do Milk Components Promote Immune Homeostasis?
Systemic Responses; the Gut–Lung Axis
Concluding Remarks
Author Contributions
Conflict of Interest Statement
Acknowledgments
References
Abstract
During the last decades, the world has witnessed a dramatic increase in allergy prevalence. Epidemiological evidence shows that growing up on a farm is a protective factor, which is partly explained by the consumption of raw cow’s milk. Indeed, recent studies show inverse associations between raw cow’s milk consumption in early life and asthma, hay fever, and rhinitis. A similar association of raw cow’s milk consumption with respiratory tract infections is recently found. In line with these findings, controlled studies in infants with milk components such as lactoferrin, milk fat globule membrane, and colostrum IgG have shown to reduce respiratory infections. However, for ethical reasons, it is not possible to conduct controlled studies with raw cow’s milk in infants, so formal proof is lacking to date. Because viral respiratory tract infections and aeroallergen exposure in children may be causally linked to the development of asthma, it is of interest to investigate whether cow’s milk components can modulate human immune function in the respiratory tract and via which mechanisms. Inhaled allergens and viruses trigger local immune responses in the upper airways in both nasal and oral lymphoid tissue. The components present in raw cow’s milk are able to promote a local microenvironment in which mucosal immune responses are modified and the epithelial barrier is enforced. In addition, such responses may also be triggered in the gut after exposure to allergens and viruses in the nasal cavity that become available in the GI tract after swallowing. However, these immune cells that come into contact with cow’s milk components in the gut must recirculate into the blood and home to the (upper and lower) respiratory tract to regulate immune responses locally. Expression of the tissue homing-associated markers α4β7 and CCR9 or CCR10 on lymphocytes can be influenced by vitamin A and vitamin D3, respectively. Since both vitamins are present in milk, we speculate that raw milk may influence homing of lymphocytes to the upper respiratory tract. This review focuses on potential mechanisms via which cow’s milk or its components can influence immune function in the intestine and the upper respiratory tract. Unraveling these complex mechanisms may contribute to the development of novel dietary approaches in allergy and asthma prevention.
Introduction
In the Western world, the prevalence of chronic inflammatory diseases, including allergies, has increased dramatically in the last few decades, while the number of serious infectious diseases has declined rapidly (1). An inverse correlation, indicating a “protective effect” of infectious diseases against chronic inflammatory diseases (e.g., allergy and asthma), was postulated in 1989 by Strachan, who formulated the hygiene hypothesis (2). The hygiene hypothesis suggests that the exposure to viruses and bacteria is essential to induce a T-helper (Th)1 response, which balances the immune system and protects against Th2-mediated diseases. With the discovery of additional T cell subsets such as Th17 cells and regulatory T cells (Tregs), this paradigm had to be revised. For example, it was demonstrated that suppressive dendritic cells (DCs) induced by helminths restored the disturbed Th1/Th2 balance by induction of Tregs (3). The immune education of DCs was suggested to be an important step toward understanding the complex relation between infectious diseases and allergies (4). Th2 responses are now known to be enhanced by the production of type 2 cytokines (e.g., TSLP, IL-25, IL-33) secreted by group 2 innate lymphoid cells and epithelial cells (5, 6). Thus, different cell types are responsible for Th2-mediated diseases such as allergies. Allergy is initiated as an aberrant immune response towards a harmless antigen (allergen). Via activation of Th2 cells, the allergen triggers the production of allergen-specific IgE by B cells that binds to high-affinity FcεR1 on effector cells like mast cells and basophils. Effector cells release soluble factors (e.g. histamine) upon secondary exposure to the allergen that cause immediate type I allergic symptoms. The term “atopic march” refers to the sequence of IgE responses and clinical symptoms initiated in early life (7).