Impact of bronchial epithelium on dendritic cell migration and function: modulation by the bacterial motif KpOmpA.
Mucosal immune response depends on the surveillance network established by dendritic cells (DC), APC localized within the epithelium. Bronchial epithelial cells (BEC) play a pivotal role both in the host defense and in the pathogenesis of inflammatory airway disorders. We previously showed that the outer membrane protein A from Klebsiella pneumoniae (KpOmpA), a pathogen-associated molecular pattern (PAMP) derived from Klebsiella pneumoniae, activates BEC. In this study, we evaluated the consequences of this activation on DC traffic and functions. KpOmpA significantly increased the production of CCL2, CCL5, CXCL10, and CCL20 by BEC. Stimulation of BEC increased their chemotactic activity for monocyte-derived DC (MDDC) precursors, through CCL5 and CXCL10 secretion. BEC/MDDC precursor coculture leads to an ICAM-1-dependent accelerated differentiation and enhanced maturation of MDDC. BEC/DC interactions did not affect the capacity of DC to induce T cell proliferation. However, DC preincubated with BEC increased significantly the IL-10 production by autologous T cells. Basolateral and intraepithelial DC differently enhance IL-4 and/or IL-10 synthesis according to the condition of stimulation. In vivo, intranasal injections of KpOmpA into BALB/c mice induced the recruitment of CD11c(+) and I-A(d+) myeloid DC associated with bronchial epithelium activation as evidenced by CCL20 expression. These data show that KpOmpA-exposed BEC participate in the homeostasis of myeloid DC network, and regulate the induction of local immune response.
Pichavant
Muriel
M
Institut National de la Santé et de la Recherche Médicale (INSERM) U774, Institut Pasteur de Lille, 1 rue de Professeur Calmette, BP 245, 59019 Lille cedex, France.
Taront
Solenne
S
Jeannin
Pascale
P
Breuilh
Laëtitia
L
Charbonnier
Anne-Sophie
AS
Spriet
Corentin
C
Fourneau
Catherine
C
Corvaia
Nathalie
N
Héliot
Laurent
L
Brichet
Anne
A
Tonnel
André-Bernard
AB
Delneste
Yves
Y
Gosset
Philippe
P
D000281:Administration, Intranasal; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000276:immunology*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D039521:CD11c Antigen / Q000032:analysis; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004848:Epithelium / Q000187:drug effects / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D022423:Myeloid Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D001425:Bacterial Outer Membrane Proteins; D039521:CD11c Antigen; D018925:Chemokines; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; C111389:I-Ad antigen; D018799:Intercellular Adhesion Molecule-1; C078167:OMPA outer membrane proteins