Novel antagonist antibody to TLR3 blocks poly(I:C)-induced inflammation in vivo and in vitro

• Published in: Cellular immunology 2011, Vol.267 (1), p.9-16
• Main Authors: Bunting, Rachel A., Duffy, Karen E., Lamb, Roberta J., San Mateo, Lani R., Smalley, Karen, Raymond, Holly, Liu, Xuesong, Petley, Ted, Fisher, Jamie, Beck, Heena, Flavell, Richard A., Alexopoulou, Lena, Ward, Christine K.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - immunology; Cell Line; Cells, Cultured; Humans; Inflammation - immunology; Intracellular Space - immunology; Macrophages - immunology; Mice; Mice, Inbred C57BL; Monoclonal antibody; Poly I-C - immunology; Poly(I:C); TLR3; Toll-Like Receptor 3 - genetics; Toll-Like Receptor 3 - immunology
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2010.10.008

Toll-like receptor 3 (TLR3) binds and signals in response to dsRNA and poly(I:C), a synthetic double stranded RNA analog. Activation of TLR3 triggers innate responses that may play a protective or detrimental role in viral infections or in immune-mediated inflammatory diseases through amplification of inflammation. Two monoclonal antibodies, CNTO4685 (rat anti-mouse TLR3) and CNTO5429 (CDRs from CNTO4685 grafted onto a mouse IgG1 scaffold) were generated and characterized. These mAbs bind the extracellular domain of mouse TLR3, inhibit poly(I:C)-induced activation of HEK293T cells transfected with mTLR3, and reduce poly(I:C)-induced production of CCL2 and CXCL10 by primary mouse embryonic fibroblasts. CNTO5429 decreased serum IL-6 and TNFα levels post-intraperitoneal poly(I:C) administration, demonstrating in vivo activity. In summary, specific anti-mTLR3 mAbs have been generated to assess TLR3 antagonism in mouse models of inflammation.