Innate immune responses and neuroepithelial degeneration and regeneration in the mouse olfactory mucosa induced by intranasal administration of Poly(I:C)

Abstract

The pathogenesis of postviral olfactory disorder (PVOD) has not been fully elucidated. We investigated morphological changes and innate immune responses in the mouse olfactory mucosa induced by intranasal administration of polyinosinic-polycytidylic acid [Poly(I:C)], a synthetic analog of viral double-stranded RNA. Mice received three administrations of saline with or without Poly(I:C), once every 24 h. The olfactory mucosa was harvested at various intervals after the first administration (8 h, 3, 9 and 24 days). In the Poly(I:C) group, the number of apoptotic cells in the olfactory neuroepithelium had increased at 8 h. At 9 days, the olfactory neuroepithelium had severely degenerated and behavioral tests demonstrated that the mice showed signs of olfactory deterioration. At 24 days, the structure of the neuroepithelium had regenerated almost completely. Regarding the innate immune responses, many neutrophils had infiltrated the olfactory neuroepithelium at 8 h and had exuded into the nasal cavity by 3 days. Macrophages had also infiltrated the olfactory neuroepithelium at 8 h although to a lesser extent, but they still remained in the neuroepithelium at 24 days. Poly(I:C)-induced neuroepithelial damage was significantly inhibited by a neutrophil elastase inhibitor and was suppressed in neutropenic model mice. These findings suggest that the secondary damage caused by the neutrophil-mediated innate immune response plays an important role in the pathogenesis of PVOD.

Environmental Toxicants-Induced Immune Responses in the Olfactory Mucosa

“…Olfactory loss in rhinitis/sinusitis is attributable primarily to blockade of airflow to the olfactory sensory neurons (OSNs) that receive odorous molecules, but damage to the OM is also considered as a possible cause (2, 4–6). In fact, multiple studies have shown that olfactory inflammation causes the loss of OSNs (7–14). …”

“…We, therefore, believe that a better understanding of the olfactory immune system will advance our knowledge of the pathogenesis and progression of neurological disease. To date, there are many reports showing that artificially induced olfactory inflammation can cause immune responses and damage to the OM (7–14). Conversely, new OSNs are generated in the OM throughout life, which may help in the repair of damaged tissue (30, 31).…”

Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis

“…The dose of poly(I:C) used was determined from the doses used in previous studies of respiratory mucosa [24,25] . The control rats received saline alone in the same manner (this experimental group was designated as the CON or IgAN group).…”

“…Lysates of cultured cells were prepared as previously described [24] . After centrifugation, the protein level was determined in supernatants using a micro BCA protein assay kit with bovine serum albumin as a standard (Pierce, Thermo).…”

“…All tonsil and spleen stainings were performed on 4-μm paraffin sections as previously described [24] . In brief, immunohistochemical stains were performed on formalin-fixed, paraffin-embedded 4-μm sections.…”