Toll-like receptor 4 plays an important role to enhance bacterial clearance from the nose in synergy with triggering receptor expressed on myeloid cells (TREM)-1 expression on polymorphonuclear neutrophils
Toll-like receptor 4 plays an important role to enhance bacterial clearance from the nose in synergy with triggering receptor expressed on myeloid cells (TREM)-1 expression on polymorphonuclear neutrophils
复制标题
DOI：
10.1016/j.ijporl.2018.06.025
复制
发表时间：
2018-09-01
影响因子：
1.5
通讯作者：
Suzuki, Masashi
中科院分区：
文献类型：
--
作者：
Moriyama, Munehito;Hirano, Takashi;Suzuki, Masashi
目的：急性鼻窦炎（ARS）是最常见的感染性疾病之一。中性粒细胞在宿主对病原微生物如真菌和细菌的先天防御中起主要作用。最近，在中性粒细胞中，发现髓样细胞上表达的触发受体（TREM）-1的连接激活全谱中性粒细胞效应器机制，包括与Toll样受体（TLR）协同的炎症介质的释放、脱粒、吞噬作用和氧化爆发。在这项研究中，我们研究了TREM-1对中性粒细胞的功能与TLR 4在鼻腔和鼻咽炎症小鼠模型通过nontypeable流感嗜血杆菌（NTHi）鼻内intravenousinsulines.Methods的影响：我们使用C3 H/HeJ（TLR 4缺陷）小鼠，自发产生，并有非功能性TLR 4蛋白，和正常野生型（WT）C3 H/HeN小鼠。将小鼠鼻内接种NTHi（10（7）cfu/小鼠）以研究TLR 4对中性粒细胞功能的影响。我们研究了接种后6、12、24和72 h鼻洗液中细菌清除和炎性细胞浸润的动力学。结果：WT小鼠鼻洗液中NTHi的细菌计数显著低于TLR 4突变小鼠。在接种后6 h、12 h和24 h，WT小鼠鼻洗液中的炎性细胞数量显著高于TLR 4缺陷型小鼠。WT小鼠中性粒细胞上TREM-1蛋白的表达和mRNA水平高于TLR 4突变小鼠。结论：TREM-1可能与TLR 4共同参与中性粒细胞对鼻咽部NTHi的清除。进一步的研究将需要阐明中性粒细胞通过TLR 4的先天免疫应答，以防止NTHi感染。
Objective: Acute rhinosinusitis (ARS) is among the most common infectious diseases. Neutrophils play a major role in innate host defenses against pathogenic microorganisms such as fungi and bacteria. Recently, in neutrophils, ligation of the triggering receptor expressed on myeloid cells (TREM)-1 was found to activate the full spectrum of neutrophil effector mechanisms, including the release of inflammatory mediators, degranulation, phagocytosis, and oxidative burst in synergy with Toll-like receptors (TLRs). In this study, we investigated the effect of TREM-1 on the functions of neutrophils in relation to TLR4 in a nasal and nasopharyngeal inflammation mouse model via nontypeable Haemophilus influenzae (NTHi) intranasal inoculation.Methods: We used C3H/HeJ (TLR4-deficient) mice, which arose spontaneously and have non-functional TLR4 protein, and normal wild-type (WT) C3H/HeN mice. Mice were inoculated intranasally with NTHi (10(7) cfu/mouse) to investigate the effects of TLR4 on the function of Neutrophils. We examined the kinetics of bacterial clearance and inflammatory cell infiltration in nasal washes at 6, 12, 24, and 72 h after inoculation. The expression of TREM-1 on neutrophils, and TREM-1 mRNA expression in neutrophils in the nasal washes were examined by flow cytometric analysis and RT-PCR.Results: Bacterial counts of NTHi from nasal washes were significantly lower in WT mice than in TLR4-mutant mice after inoculation. The numbers of inflammatory cells in nasal washes were significantly higher in WT mice at 6 h, 12 h, and 24 h after inoculation than in TLR4-deficient mice. The expression of TREM-1 protein on neutrophils and the mRNA levels were greater in WT mice than in TLR4-mutant mice. The concentrations of soluble TREM-1 in WT nasal washes were also significantly higher than in those of TLR4-deficient mice.Conclusion: TREM-1 may play an important role together with TLR4 in the nasopharyngeal clearance of NTHi by neutrophils. Further studies will need to clarify the innate immune responses of neutrophils via TLR4 to prevent NTHi infection.