Early bacterial colonization induces toll-like receptor-dependent transforming growth factor beta signaling in the epithelium.
Colonization of the upper respiratory tract is an initial step that may lead to disease for many pathogens. To prevent compromise of the epithelial barrier, the host must monitor and tightly control bacterial levels on the mucosa. Here we show that innate immune functions of respiratory epithelial cells control colonization by Streptococcus pneumoniae and Haemophilus influenzae in a Toll-like receptor (TLR)-dependent manner. Activation of inflammatory pathways, including mitogen-activated protein kinase signaling, in respiratory epithelial cells was accompanied by the induction of the transforming growth factor beta signaling cascade during early colonization. Thus, colonization resulted in upregulation of factors involved in a proinflammatory response (e.g., interleukin-6) as well as factors known to modulate the epithelial barrier (e.g., Snail-1). These in vivo data provided a link between inflammation control and maintenance of the mucosal barrier function during infection and emphasized the importance of TLR-dependent inflammatory responses of the respiratory epithelium.
Beisswenger
Christoph
C
402A Johnson Pavilion, Department of Microbiology and Pediatrics, University of Pennsylvania, Philadelphia, PA 19104-6076, USA. weiser@mail.med.upenn.edu
Lysenko
Elena S
ES
Weiser
Jeffrey N
JN
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004848:Epithelium / Q000276:immunology* / Q000382:microbiology; D005260:Female; D006193:Haemophilus influenzae / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009305:Nasopharynx / Q000276:immunology / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000276:immunology*; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*
D016207:Cytokines; D051193:Toll-Like Receptors; D016212:Transforming Growth Factor beta