Lipooligosaccharide from Bordetella pertussis induces mature human monocyte-derived dendritic cells and drives a Th2 biased response.
Bordetella pertussis has a distinctive cell wall lipooligosaccharide (LOS) that is released from the bacterium during bacterial division and killing. LOS directly participates in host-bacterial interactions, in particular influencing the dendritic cells' (DC) immune regulatory ability. We analyze LOS mediated toll-like receptor (TLR) activation and dissect the role played by LOS on human monocyte-derived (MD)DC functions and polarization of the host T cell response. LOS activates TLR4-dependent signaling and induces mature MDDC able to secrete IL-10. LOS-matured MDDC enhance allogeneic presentation and skew T helper (Th) cell polarization towards a Th2 phenotype. LOS protects MDDC from undergoing apoptosis, prolonging their longevity and their functions. Compared to Escherichia coli lipopolysaccharide (LPS), the classical DC maturation stimulus, LOS was a less efficient inducer of TLR4 signaling, MDDC maturation, IL-10 secretion and allogeneic T cell proliferation and it was not able to induce IL-12p70 production in MDDC. However, the MDDC apoptosis protection exerted by LOS and LPS were comparable. In conclusion, LOS treated MDDC are able to perform antigen presentation in a context that promotes licensing of Th2 effectors. Considering these properties, the use of LOS in the formulation of acellular pertussis vaccines to potentiate protective and adjuvant capacity should be taken into consideration.
Fedele
Giorgio
G
Department of Infectious, Parasitic and Immune-mediated Diseases, Anti-infectious Immunity Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Celestino
Ignacio
I
Spensieri
Fabiana
F
Frasca
Loredana
L
Nasso
Maria
M
Watanabe
Mineo
M
Remoli
Maria Elena
ME
Coccia
Eliana Marina
EM
Altieri
Fabio
F
Ausiello
Clara Maria
CM
D017209:Apoptosis / Q000276:immunology; D001886:Bordetella pertussis / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D018418:Th2 Cells / Q000276:immunology* / Q000382:microbiology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D010566:Virulence Factors, Bordetella / Q000276:immunology* / Q000494:pharmacology; D014917:Whooping Cough / Q000276:immunology* / Q000382:microbiology
D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D010566:Virulence Factors, Bordetella; C084764:pertussis endotoxin; D016753:Interleukin-10; D012313:RNA