Komai-Koma Mousa, Li Dong, Wang Eryi, Vaughan Diane, Xu Damo
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Immunology. 2014 Nov;143(3):354-62. doi: 10.1111/imm.12312.
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.
Toll样受体（TLRs）2和4识别不同的内源性和外源性激动剂，并在感染和炎症中发挥不同作用。然而，它们在特定感染性和炎症性疾病中的最终作用尚不太清楚。我们制备了多克隆抗小鼠TLR2和TLR4抗体，并研究了它们对皮肤利什曼病和炎性关节炎的作用。与用对照IgG处理的小鼠相比，将这些抗体给予在足垫感染了硕大利什曼原虫的易感BALB/c小鼠，可减轻足垫肿胀，但不能降低寄生虫负荷。这些抗体协同降低了感染小鼠中利什曼原虫特异性T细胞增殖、1型和2型辅助性T细胞细胞因子产生、特异性IgG1和IgG2a抗体合成以及树突状细胞上T细胞受体和共刺激分子的表达。然后，我们测试了这些抗体对DBA/1小鼠胶原诱导性关节炎（CIA）的作用，CIA是一种慢性炎症的经典模型。两种抗体均显著抑制临床参数的发展，同时降低促炎细胞因子的产生。因此，这些数据表明抗TLR2和4抗体可能在体内对炎症性疾病具有协同治疗作用。
