Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin.
Bacterial products (such as endotoxins and flagellin) trigger innate immune responses through TLRs. Flagellin-induced signalling involves TLR5 and MyD88 and, according to some reports, TLR4. Whereas epithelial and dendritic cells are stimulated by flagellin in vitro, the cell contribution to the in vivo response is still unclear. Here, we studied the respective roles of radioresistant and radiosensitive cells in flagellin-induced airway inflammation in mice. We found that i.n. delivery of flagellin elicits a transient change in respiratory function and an acute, pro-inflammatory response in the lungs, characterized by TLR5- and MyD88-dependent chemokine secretion and neutrophil recruitment. In contrast, TLR4, CD14 and TRIF were not essential for flagellin-mediated responses, indicating that TLR4 does not cooperate with TLR5 in the lungs. Respiratory function, chemokine secretion and airway infiltration by neutrophils were dependent on radioresistant, TLR5-expressing cells. Furthermore, lung haematopoietic cells also responded to flagellin by activating TNF-alpha production. We suggest that the radioresistant lung epithelial cells are essential for initiating early, TLR5-dependent signalling in response to flagellin and thus triggering the lung's innate immune responses.
Janot
Laure
L
University of Orleans and CNRS, Molecular Immunology and Embryology, UMR 6218, Institut de Transgénose, Orléans, France.
Sirard
Jean-Claude
JC
Secher
Thomas
T
Noulin
Nicolas
N
Fick
Lizette
L
Akira
Shizuo
S
Uematsu
Satoshi
S
Didierlaurent
Arnaud
A
Hussell
Tracy
T
Ryffel
Bernhard
B
Erard
Francois
F
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D000281:Administration, Intranasal; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D005408:Flagellin / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D009504:Neutrophils / Q000166:cytology; D009195:Peroxidase / Q000378:metabolism; D010993:Plethysmography, Whole Body; D011828:Radiation Chimera / Q000276:immunology / Q000378:metabolism; D011836:Radiation Tolerance; D020545:Respiratory Mucosa / Q000276:immunology*; D051198:Toll-Like Receptor 5 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; D018925:Chemokines; D016207:Cytokines; D005408:Flagellin; D053594:Myeloid Differentiation Factor 88; D009195:Peroxidase; D051198:Toll-Like Receptor 5; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse