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Identification of a TLR-independent pathway for Borrelia burgdorferi-induced expression of matrix metalloproteinases and inflammatory mediators through binding to integrin alpha 3 beta 1. J Immunol 2006 Jul 01;177(1):657-64 PMID: 16785564

Pubmed ID

16785564

Abstract

Borrelia burgdorferi stimulates a robust inflammatory response at sites of localization. Binding of borrelial lipoproteins to TLR-2 is one pathway important in the host response to B. burgdorferi. However, while TLR-2 is clearly important in control of infection, inflammation is actually worsened in the absence of TLR-2 or the shared TLR adapter molecule, MyD88, suggesting that there are alternative pathways regulating inflammation. Integrins are cell surface receptors that play an important role in cell to cell communications and that can activate inflammatory signaling pathways. In this study, we report for the first time that B. burgdorferi binds to integrin alpha(3)beta(1) and that binding of B. burgdorferi to this integrin results in induction of proinflammatory cytokines, chemokines, and end-effector molecules such as matrix metalloproteinases in primary human chondrocyte cells. Expression of these same molecules is not affected by the absence of MyD88 in murine articular cartilage, suggesting that the two pathways act independently in activating host inflammatory responses to B. burgdorferi. B. burgdorferi-induced alpha(3) signaling is mediated by JNK, but not p38 MAPK. In summary, we have identified a new host receptor for B. burgdorferi, integrin alpha(3)beta(1); binding of B. burgdorferi to integrin alpha(3)beta(1) results in the release of inflammatory mediators and is proposed as a TLR-independent pathway for activation of the innate immune response by the organism.

Author List

Behera AK, Hildebrand E, Uematsu S, Akira S, Coburn J, Hu LT

Author

Jenifer Coburn PhD Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-33745320471   45 Citations

MESH terms used to index this publication - Major topics in bold

Adaptor Proteins, Signal Transducing
Animals
Bacterial Adhesion
Borrelia Infections
Borrelia burgdorferi
Cells, Cultured
Chemokines
Chondrocytes
Cytokines
Humans
Inflammation Mediators
Integrin alpha3beta1
Integrin beta Chains
Matrix Metalloproteinase 1
Matrix Metalloproteinase 3
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88
Signal Transduction
Toll-Like Receptor 2
jenkins-FCD Prod-331 a335b1a6d1e9c32173c9534e6f6ff51494143916