Alloiococcus otitidis is a ligand for collectins and Toll-like receptor 2, and its phagocytosis is enhanced by collectins.
Alloiococcus otitidis has been found to be associated with otitis media with effusion. In this study we investigated whether TLR2 and collectins, surfactant protein A (SP-A) and mannose-binding lectin (MBL), interacted with A. otitidis. Both SP-A and MBL bound to A. otitidis in a Ca(2+)-dependent manner. A. otitidis induced IL-8 secretion from U937 cells and NF-kappaB activation in TLR2-transfected HEK293 cells. However, the cells transfected with the mutant TLR2(P681H) did not respond to A. otitidis. In addition, A. otitidis co-sedimented a recombinant soluble form of the extracellular TLR2 domain, indicating direct binding of the bacterium to TLR2. SP-A and MBL augmented the phagocytosis of A. otitidis by J774A.1 cells. The collectin-stimulated phagocytosis of A. otitidis was significantly attenuated when fucoidan and polyinosinic acid were co-incubated. Immunoblotting analysis revealed that MBL was present in the middle ear effusion from patients with otitis media. These results demonstrate that A. otitidis is a ligand for the collectins and TLR2, and that the collectins enhance the phagocytosis of A. otitidis by macrophages, suggesting important roles of the collectins and TLR2 in the innate immunity of the middle ear against A. otitidis infection.
Konishi
Masanori
M
Department of Biochemistry, Sapporo Medical University School of Medicine, Japan.
Nishitani
Chiaki
C
Mitsuzawa
Hiroaki
H
Shimizu
Takeyuki
T
Sano
Hitomi
H
Harimaya
Atsushi
A
Fujii
Nobuhiro
N
Himi
Tetsuo
T
Kuroki
Yoshio
Y
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000276:immunology / Q000378:metabolism*; D016908:Gram-Positive Bacterial Infections / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D037601:Mannose-Binding Lectin / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D010034:Otitis Media with Effusion / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D011069:Poly I / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*; D020298:U937 Cells
D000900:Anti-Bacterial Agents; D016209:Interleukin-8; D008024:Ligands; D037601:Mannose-Binding Lectin; D016328:NF-kappa B; D011134:Polysaccharides; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D011069:Poly I; C007789:fucoidan