|Reference : Etude du rôle des macrophages interstitiels dans l'allergie des voies respiratoires|
|Dissertations and theses : Doctoral thesis|
|Life sciences : Veterinary medicine & animal health|
|Etude du rôle des macrophages interstitiels dans l'allergie des voies respiratoires|
|[en] Study of the role of interstitial macrophages in airway allergy|
|Bedoret, Denis [Université de Liège - ULg > Département de sciences fonctionnelles > Physiologie >]|
|Université de Liège, Belgium|
|Doctorat en Sciences vétérinaires|
|133 + 53|
|[en] Asthma ; Allergy ; Macrophage ; Dendritic cell ; Endotxin|
|[en] Respiratory mucosal surfaces are constantly exposed to a broad range of non-pathogenic environmental antigens. In the absence of proinflammatory signals, inhalation of harmless antigens results in immunological tolerance. Indeed, lung dendritic cells stimulate the development of antigen-specific regulatory T cells. Nevertheless, epidemiological studies have shown that ambient air contains not only inert antigens but also immunostimulatory molecules of microbial origin. Of particular interest are endotoxins, a cell wall component of gram-negative bacteria that is ubiquitous in the environment. In spite of the fact that high levels of endotoxin exposure in early life protect against allergic sensitization, most evidence indicates that exposure to house-dust endotoxin is a significant risk factor for increased asthma prevalence and severity. When the respiratory tract is stimulated with airborne endotoxins, lung dendritic cells lose their tolerogenic properties and rather promote the development of an allergic response directed against concomitant aeroantigens. Although endotoxins are omnipresent in the environment and favour airway allergy, only a minority of people develops asthma. A unifying model reconciling these conflicting observations is still lacking. We report here that LPS-triggered airway allergy is tightly controlled by lung interstitial macrophages, a cell population that remains largely uncharacterized. Interstitial macrophages could be distinguished from alveolar macrophages by their unique capacity to inhibit lung dendritic cell maturation and migration upon LPS stimulation, thereby preventing sensitization to concomitant inhaled antigens. We furthermore demonstrated that functional paralysis of LPS-stimulated dendritic cells involves interleukin-10 production by interstitial macrophages. Finally, we demonstrate that specific in vivo elimination of interstitial macrophages leads to overt asthmatic reactions to innocuous airborne antigens inhaled along with low LPS doses. Our study thus reveals a crucial role for interstitial macrophages in maintaining immune homeostasis in the respiratory tract and provides an explanation for the paradox that airborne LPS has the ability to promote the induction of Th2 responses by lung dendritic cells but does not provoke airway allergy under normal conditions. In the presence of LPS, interstitial macrophages, but not alveolar macrophages, break the link between innate and adaptive immunity, allowing harmless inhaled antigens to escape from T cell-dependent responses.|
|Giga-Infection, Immunity and Inflammation|
|Researchers ; Professionals ; Students|
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