Basophil activation through TLR2 and TLR4 signaling pathways

Autor: Abdulraouf Ramadan, Elke Schneider, Nathalie Thieblemont, François Machavoine, Manal Alkan, Michel Dy, Fadel Sayes
Přispěvatelé: Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cytokines, hématopoïèse et réponse immune (CHRI), LabEx Inflamex, This work was supported by individual funding, as follows: CNRS (PEPS, N Thieblemont), Labex Inflamex, the Chancellerie des Universités de Paris (Legs Poix, N. Thieblemont). Manal Alkan was supported by the Syrian government (PhD fellowship) and by the Fondation pour la Recherche Médicale (FRM)., The authors acknowledge Muriel Andrieu and Karine Labroquère of the Cochin Cytometry and Immunobiology Facility, Agnès Lebon and the staff of the Animal Care Facilities at the Cochin Institute, Martine Caroff (Orsay, France), Armelle Blondel (Institut Cochin, Paris, France), and Jean-Marc Cavaillon (Institut Pasteur, Paris, France) providing reagents and for their assistance in experimental studies, Shizuo Akira (Japan) for providing mice, the assistance of Jean Fioramonti providing crude extract of parasite (INRA, Toulouse, France), and the excellent technical assistance of Céline Dietrich for some in vitro experiments., ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2018
Předmět:
Zdroj: AIMS Allergy and Immunology
AIMS Allergy and Immunology, AIMS Press, 2018, Basophils, 2 (3), pp.126-140. ⟨10.3934/Allergy.2018.3.126⟩
AIMS Allergy and Immunology, Vol 2, Iss 3, Pp 126-140 (2018)
ISSN: 2575-615X
DOI: 10.3934/allergy.2018.3.126
Popis: Basophils are effector cells that respond to protease allergens and parasites, thus contributing to allergic inflammation and Th2 differentiation. However, the molecular interactions through which pathogens promote activation as well as recruitment of these cells to sites of inflammation remain poorly understood. We found that administration of extracts from Nippostrongylus brasiliensis induced both basophil recruitment into blood and liver in vivo and IL-4 and histamine production by purified bone marrow-derived basophils in vitro. Starting from this finding, we set out to identify putative pathogen-derived molecules for their capacity to activate murine basophils, using a basophil population differentiated and expanded from bone marrow cells cultured with IL-3 and sorted as a CD49b+ c-kit– subset. Among a number of Toll-like receptor (TLR) agonists tested, we found that the lipopeptide Pam2CSK4 and lipopolysaccharide (LPS) activate basophils in terms of IL-4, IL-6 and histamine production through TLR2 and TLR4, respectively. By contrast, TLR3 or TLR7 agonists had no such effect. We further identified nitric oxide (NO) as key mediator for LPS stimulation and established that in vivo administration of LPS led to basophil recruitment into the liver. Our results reveal the important contribution of MyD88 and NO signaling to antigen recognition through TLR2 and TLR4 pathways leading to activation, degranulation and release of immunoregulatory mediators.
Databáze: OpenAIRE