Viral disruption of olfactory progenitors is exacerbated in allergic mice

Abstract

Upper airway viral infection in patients with airway allergy often exacerbates olfactory dysfunction, but the mechanism for this exacerbation remains unclear. Here, we examined the effects of respiratory syncytial virus (RSV) infection, in the presence or absence of airway allergy, on olfactory receptor neurons (ORNs) and their progenitors in mice. Immunohistological analyses revealed that cockroach allergen (CRA)-induced airway allergy alone did not affect the number of OMP+ mature ORNs and SOX2+ ORN progenitors. Intranasal RSV line 19 infection in allergy-free mice resulted in a transient decrease in SOX2+ ORN progenitors without affecting OMP+ ORNs. In contrast, the RSV-induced decrease in SOX2+ ORN progenitors was exacerbated and prolonged in allergic mice, which resulted in eventual loss of OMP+ ORNs. In the allergic mice, reduction of RSV in the olfactory epithelium was delayed as compared with allergy-free mice. These results suggest that ORN progenitors were impaired by RSV infection and that airway allergy exacerbated damage to ORN progenitors by reducing viral clearance.

Effects of Cigarette Smoke on the Nasal Respiratory and Olfactory Mucosa in Allergic Rhinitis Mice

“…In addition, more frequent or higher dose administration of CSS may cause extensive impairment of the OE even in allergic mice, as long-term CSS exposure damaged olfactory progenitors and decreased mature ORNs, resulting in deterioration of olfaction (Ueha et al, 2016a). Regarding tissue change in the OE of allergic rhinitis mice, as all previous studies focused on the OE of the NS, and not on the UL part of the OE (Ozaki et al, 2010;Carr et al, 2012;Ueha et al, 2014), the lateral area of the OE should be included in further investigations.…”

“…As previously described (Ueha et al, 2014(Ueha et al, , 2016a(Ueha et al, , 2018bNishijima et al, 2016), all samples were cut at the level of the incisive papilla of the hard palate in coronal sections for examinations of the RM (Nishijima et al, 2016), and were cut from the level of the anterior end of the olfactory bulb to the 1-mm anterior level for examinations of the OE (Ueha et al, 2014(Ueha et al, , 2016a(Ueha et al, , 2018b. Four-micrometer thick paraffin sections were deparaffinized in xylene and rehydrated in ethanol before hematoxylin and eosin staining for evaluation of whole tissue structure, Sirius red staining for eosinophils, periodic acid-Schiff and Alcian blue (PAS/AB) staining for goblet cells, and immunostaining.…”

“…Before investigating the CSS effects on the OE in allergic mice, we preliminary verified whether repetitive OVA-immunization damaged the OE. Although we previously reported that a cockroach allergen did not affect the number of OMP + mature ORNs (Ueha et al, 2014), the examined area was restricted to the OE of the nasal septum. As the ORNs in the OE differ according to their zonal expression patterns, in the present study, we investigated the number of ORNs in the OE of three different areas; nasal septum (NS), named "upper-lateral area" (UL), and "uppermost-lateral area" (UML) (Figure 6A-a).…”

Reduction of Proliferating Olfactory Cells and Low Expression of Extracellular Matrix Genes Are Hallmarks of the Aged Olfactory Mucosa

“…Neurogenesis was examined following previously described methods (Buckland and Cunningham, 1999 ; Ueha et al, 2014 , 2016a , b ); tissues were stained with the following anti-mouse primary antibodies: SOX2 (1:300 dilution; rabbit monoclonal, Abcam clone EPR3131; Cambridge, UK), GAP43 (1:1,000 dilution; rabbit polyclonal, NOVUS #NB300-143B; Littleton, CO, USA), Ki-67 (1:200 dilution; rabbit monoclonal, Novus #NB600-1252), OMP (olfactory marker protein; 1:8,000 dilution, goat polyclonal, Wako), and cleaved caspase-3 (1:300 dilution; rabbit polyclonal, Cell Signaling #9661; Danvers, MA, USA). SRY (sex determining region Y)-box 2 (SOX2) is a transcription factor that is widely expressed in stem cell populations and is involved in maintaining the undifferentiated state.…”

“…The olfactory mucosa consists of the OE and lamina propria. The OE of the olfactory mucosa has a unique regenerative stem cell system; it is maintained by the life-long replenishment of mature ORNs in the luminal layer from the stem/progenitor cells in the basal layer (Costanzo, 1991 ; Schwob, 2002 ; Su et al, 2009 ; Ueha et al, 2014 ). During steady-state neurogenesis, primitive olfactory progenitor cells differentiate into late progenitor cells, which subsequently differentiate into immature ORNs.…”