How Loss of Bacterial Symbionts Promotes Development of Allergies & acts on Immune System Balance

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The presence of microbes specifically blocks the immune cells responsible for triggering allergies. It is well known the microbiota is involved in many mechanisms, including digestion, vitamin synthesis and host defense.The hygiene hypothesis suggests a link between a decline in infectious diseases and increase in allergic diseases in industrialized countries. Improvements in hygiene levels lead to reduced contact with microbes that is paralleled by an increased incidence in allergic and autoimmune diseases, eg type 1 diabetes.

Epidemiological studies have substantiated this hypothesis, by showing children living with farm animals – and thus with more microbial agents – develop fewer allergies during their lifetime. Conversely, administering antibiotics to mice within the 1st days of life results in a loss of microbiota, and an increased incidence in allergy. However, until now, the biological mechanisms remained unclear. In this study, Gérard Eberl’s team show that in mice, symbiotic intestinal microbes act on the immune system by blocking allergic reactions.

Bacterial or fungal microbes provoke type 3 cell response from immune cells >>coordinate phagocytosis and killing of microbes. But, in the case of infection by pathogenic agents that are too large to be handled by type 3 cells (eg parasitic worms and certain allergens), the cells that organize the elimination of the pathogen, but also allergic reactions, are known as type2 cells. Institut Pasteur researchers show type 3 cells activated during a microbial aggression inhibit type 2 activity >>thus no allergic immune responses. ie microbiota indirectly regulates type 2 immune responses by inducing type 3 cells.

>>ie microbiota-induced Tregs (regulatory T cells) express the nuclear hormone receptor RORγt and differentiate along a pathway that also leads to Th17 cells. In the absence of RORγt+ Tregs, Th2-driven defense against helminths is more efficient while Th2-associated pathology is exacerbated. Thus, microbiota regulates type 2 responses through induction of “type 3” RORγt+ Tregs and Th17 cells and acts as a key factor in balancing immune responses at mucosal surfaces.

>>Imbalance in microbiota triggers exaggerated type 2 immune response normally used to fight large parasites, but also leads to allergic responses.
Rx option: stimulating type 3 cells by mimicking a microbial antigen in order to block allergy-causing type 2 cells. http://www.pasteur.fr/en/institut-pasteur/press/press-documents/role-microbiota-preventing-allergies

A cluster of type 3 cells (shown in green) in a mouse colon. These cells are induced by the microbiota and block type 2 allergic reactions. Credit: © Institut Pasteur

A cluster of type 3 cells (shown in green) in a mouse colon. These cells are induced by the microbiota and block type 2 allergic reactions.
Credit: © Institut Pasteur