Oral Tolerance and Allergic Responses to Food Proteins
Oral Tolerance and Allergic Responses to Food Proteins
Purpose of Review: The default response to protein antigens in the intestine is the induction of systemic and local hyporesponsiveness, ensuring the prevention of coeliac disease and food allergies. Interest is increasing in the role of dietary manipulation and probiotics in treating allergic and other diseases, but less is known about how these regimens might influence systemic and local immune responses. This paper addresses the mechanisms at the interface of innate and adaptive immunity that determine how the body responds to orally administered proteins and how local bacteria modify these.
Recent Findings: This paper discusses evidence that dendritic cells in the intestinal mucosa are the critical cells that take up dietary proteins and migrate to the draining mesenteric lymph node, where they induce regulatory CD4 T-cell differentiation. The properties of tolerized T cells are discussed and it is proposed that the gut microenvironment maintains homeostasis by conditioning dendritic cells to remain in a quiescent state. Inhibitory signalling by commensal bacteria possibly contributes to this process.
Summary: A regulatory network controls how dietary antigens are taken up and presented to T lymphocytes by specialized antigen-presenting cells. Elucidating their nature and how they are influenced by external factors such as probiotics may help develop novel therapies for allergy and help understand diseases such as coeliac disease.
Administration of antigen by the oral route induces hyporesponsiveness to subsequent challenge with the antigen given in an immunogenic form, a phenomenon termed oral tolerance (see Mowat et al., Faria and Weiner, and Smith and Nagler-Anderson for reviews). Described at the beginning of the 20th century by Wells and Osborne, it usually refers to how a prior feed of antigen can modify systemic immune responses to antigenic challenge given by a parenteral route. There is ample evidence, however, that oral tolerance also affects the responsiveness of the local immune system in the intestinal mucosa itself, thus preventing hypersensitivity reactions to food proteins that could otherwise lead to disorders such as coeliac disease or food allergies.
The state of tolerance induced by feeding antigens contrasts with the active immune responses needed to protect the gut against continual bombardment by invasive pathogens or their products. Here we discuss the most recent advances in our understanding of oral tolerance to protein antigens, the interactions between the innate and adaptive immune system, and the way in which intestinal microbiota may affect the outcome of intestinal antigen exposure.
Abstract and Introduction
Abstract
Purpose of Review: The default response to protein antigens in the intestine is the induction of systemic and local hyporesponsiveness, ensuring the prevention of coeliac disease and food allergies. Interest is increasing in the role of dietary manipulation and probiotics in treating allergic and other diseases, but less is known about how these regimens might influence systemic and local immune responses. This paper addresses the mechanisms at the interface of innate and adaptive immunity that determine how the body responds to orally administered proteins and how local bacteria modify these.
Recent Findings: This paper discusses evidence that dendritic cells in the intestinal mucosa are the critical cells that take up dietary proteins and migrate to the draining mesenteric lymph node, where they induce regulatory CD4 T-cell differentiation. The properties of tolerized T cells are discussed and it is proposed that the gut microenvironment maintains homeostasis by conditioning dendritic cells to remain in a quiescent state. Inhibitory signalling by commensal bacteria possibly contributes to this process.
Summary: A regulatory network controls how dietary antigens are taken up and presented to T lymphocytes by specialized antigen-presenting cells. Elucidating their nature and how they are influenced by external factors such as probiotics may help develop novel therapies for allergy and help understand diseases such as coeliac disease.
Introduction
Administration of antigen by the oral route induces hyporesponsiveness to subsequent challenge with the antigen given in an immunogenic form, a phenomenon termed oral tolerance (see Mowat et al., Faria and Weiner, and Smith and Nagler-Anderson for reviews). Described at the beginning of the 20th century by Wells and Osborne, it usually refers to how a prior feed of antigen can modify systemic immune responses to antigenic challenge given by a parenteral route. There is ample evidence, however, that oral tolerance also affects the responsiveness of the local immune system in the intestinal mucosa itself, thus preventing hypersensitivity reactions to food proteins that could otherwise lead to disorders such as coeliac disease or food allergies.
The state of tolerance induced by feeding antigens contrasts with the active immune responses needed to protect the gut against continual bombardment by invasive pathogens or their products. Here we discuss the most recent advances in our understanding of oral tolerance to protein antigens, the interactions between the innate and adaptive immune system, and the way in which intestinal microbiota may affect the outcome of intestinal antigen exposure.
