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.

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 (107 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.