Cellules dendritiques et Toll-like récepteurs dans les maladies allergiques

Bronchial airways represent a major portal of entry for pathogenic microorganisms and allergens, and they are equipped with a dual response system: innate immunity and adaptative immunity. The innate defense system is composed of phagocytic cells [(alveolar macrophages, neutrophils and dendritic cells (DCs)]. These cells express pattern recognition receptors (PRRs) that directly recognize pathogen-associated molecular patterns (PAMPs), which are shared by numerous microorganisms. Among PPRs, eleven different Toll-like receptors (TLRs) are described. DCs are also engaged in the adaptive immune response, as they are able, after antigen processing, to transfer specific information to T-lymphocytes. Moreover, through the presence of TLRs -- in particular, TLR2 and TLR4 -- on their surface, DCs are at the intersection between adaptive immunity and innate immunity. After activation by certain ligands (endotoxins such as LPS, bacterial peptidoglycans, envelope proteins), DCs are able to orientate the response to allergen either to a Th1 profile or a pro-allergenic Th2 profile. Via TLRs, PAMPs are also able to directly interact with regulatory T cells, the role of which in the natural development of tolerance towards non-self proteins is now established. Several recent studies emphasize the role of TLRs in the onset and regulation of allergic diseases: the hygiene hypothesis suggests that endotoxin exposure plays a key role in the prevention of some allergic diseases; on the other hand, polymorphisms of certain PAMPs (such as those on Chlamydia pneumoniae or RSV) might favour bronchial inflammation and could explain the development of post-infectious, nonallergic (“intrinsic”) asthma. However, it is likely that the exact nature of the endotoxins, as well as the doses inhaled and also the timing of the penetration into the respiratory tract in relation to contact with allergen could explain some of the discrepancies between experimental and clinical data. Nevertheless, it is certain that the couple TLR-ligand plays a determinant role at different steps in the development of an inflammatory allergic reaction.