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Immunology. 2014 Nov;143(3):354-62. doi: 10.1111/imm.12312.

Anti-Toll-like receptor 2 and 4 antibodies suppress inflammatory response in mice.

Author information

1
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.

Abstract

Toll-like receptors (TLRs) 2 and 4 recognize different endogenous and exogenous agonists and play a distinct role in infection and inflammation. However, their ultimate effect in a given infectious and inflammatory disease is less understood. We produced polyclonal anti-murine TLR2 and TLR4 antibodies and investigated their effect on cutaneous leishmaniasis and inflammatory arthritis. Administration of these antibodies to susceptible BALB/c mice, infected in the footpad with Leishmania major, reduced footpad swelling but not the parasite load compared with mice treated with control IgG. The antibodies synergistically reduced leishmanial-specific T-cell proliferation, T helper type 1 and type 2 cytokine production, specific IgG1 and IgG2a antibody synthesis, and T-cell receptor and co-stimulatory molecule expression on dendritic cells in infected mice. We then tested the effect of these antibodies on collagen-induced arthritis (CIA) in DBA/1 mice, a classic model of chronic inflammation. Both antibodies markedly suppressed the development of clinical parameters with concomitant reduction of pro-inflammatory cytokine production. These data therefore suggest that anti-TLR2 and 4 antibodies may have a synergistic therapeutic effect on inflammatory disease in vivo.

KEYWORDS:

anti-Toll-like receptor; inflammation; leishmaniasis; rheumatoid arthritis

PMID:
24801735
PMCID:
PMC4212949
DOI:
10.1111/imm.12312
[Indexed for MEDLINE]
Free PMC Article
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