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Food allergies: the sensitization route influences the immune response

Researchers at the Laboratoire d’immuno-allergie alimentaire (LIAA, SPI/DMTS) show that the initial route of sensitization to a food allergen (oral, respiratory, cutaneous) directly influences the nature of immune responses at multiple sites in the body.

Published on 25 April 2022

Not one but multiple sensitization routes

​Food allergies correspond to inappropriate immune responses of the body to certain food proteins. They have been constantly increasing for at least 20 years and the reasons for this increase are probably multiple. One of them is related to the fact that our environment is rich in food allergens that can enter our body not only via an oral route when we ingest food but also through the respiratory tract (e.g. when cooking food) or through the skin, when the skin barrier is damaged or inflamed. This is particularly the case for people with atopic dermatitis (AD). The immune interconnections between the different mucous membranes of the body may then explain why allergic symptoms occur at distant sites. These interconnections could also participate in the "atopic march", i.e. the progression of atopic disorders from atopic dermatitis in early childhood to food allergy, allergic rhinitis and then asthma as the child grows up. Indeed, children with AD have an increased risk of developing other atopic diseases and about 35% of them will develop food allergy later in life.

There are structural and functional differences between nasopharyngeal-, skin-, or gut- associated lymphoid tissues, but it remains unclear how entry through one route or another influences subsequent allergic reactions, locally or at more distant mucosal sites. The complexity of the mechanisms that underlie allergic inflammatory responses still limits our understanding of the adverse effects that occur in individuals who suffer from allergies.

Experimental exposition

The Laboratoire d'immuno-allergie alimentaire (LIAA, SPI/DMTS) sought to further analyze the impact of the route of exposure on the cellular actors recruited at various mucosal and immune sites. Mice were exposed to major food allergens, peanut proteins (extracted from roasted peanuts), by the intragastric, respiratory or cutaneous route. In collaboration with researchers from INRAE Nantes and the Micalis Institute, the laboratory evaluated sensitization and the allergy elicitation as well as the frequency of T cells, innate lymphoid cells (ILC) and inflammatory and dendritic cells in broncho-alveolar lavages, lungs, skin, intestine and various lymph nodes. All routes of exposure, except cutaneous, induced sensitization, but intestinal allergy was induced only in intragastrically-exposed mice. Analysis of all cellular constituents did not distinguish intragastrically exposed mice from control mice. In contrast, respiratory-sensitized mice constituted a distinct cluster, characterized by high local inflammation and immune cells recruitment. Those mice also showed changes in ILCs frequencies in the intestines, at a distance from the exposure site. Despite the absence of sensitization, cutaneous-exposed mice evidenced changes comparable to those receiving peanut by the respiratory route, although less intense.  

The study, published in the journal Nutrients, highlights that the initial route of sensitization to a food allergen influences the nature of the immune responses at various mucosal sites. Interconnections of mucosal immune systems may contribute to the complexity of clinical manifestations as well as to the atopic march.

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