The SP-TLR axis, which locally primes the nasal mucosa, is impeded in patients with allergic rhinitis

Substance P (SP) and toll-like receptors (TLRs) contribute to airway disease, particularly during viral infection. We recently demonstrated that SP can act as an initial response to viral stimuli in the upper airway by upregulating TLRs in the nasal epithelia (the SP-TLR axis). Patients with allergic rhinitis (AR) suffer from prolonged airway infections. The

SP-induced regulation of TLR4 in the human nasal mucosa is disturbed in AR. An altered SP-mediated innate immune response may contribute to the dysfunctional and often prolonged responses to infection in AR.

SP stimulation of tissue from healthy volunteers resulted in a transient increase of the TLR4 expression, whereas stimulation of AR patient-derived material led to a delayed and prolonged upregulation of TLR4. NEP expression in HNEC was lower in AR than healthy controls whereas NK1 receptor expression was increased. SP pretreatment increased TLR4-dependent IL-8 expression in healthy controls, but not in AR. Conclusions: SP-induced regulation of TLR4 in the human nasal mucosa is disturbed in AR. An altered SP-mediated innate immune response may contribute to the dysfunctional and often prolonged responses to infection in AR.