Immunological status of the olfactory bulb in a murine model of Toll-like receptor 3-mediated upper respiratory tract inflammation

Abstract Background Postviral olfactory dysfunction (PVOD) following a viral upper respiratory tract infection (URI) is one of the most common causes of olfactory disorders, often lasting for over a year. To date, the molecular pathology of PVOD has not been elucidated. Methods A murine model of Toll-like receptor 3 (TLR3)-mediated upper respiratory tract inflammation was used to investigate the impact of URIs on the olfactory system. Inflammation was induced via the intranasal administration of polyinosinic–polycytidylic acid (poly(I:C), a TLR3 ligand) to the right nostril for 3 days. Peripheral olfactory sensory neurons (OSNs), immune cells in the olfactory mucosa, and glial cells in the olfactory bulb (OB) were analyzed histologically. Proinflammatory cytokines in the nasal tissue and OB were evaluated using the quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Results In the treated mice, OSNs were markedly reduced in the olfactory mucosa, and T cell and neutrophil infiltration therein was observed 1 day after the end of poly(I:C) administration. Moreover, there was a considerable increase in microglial cells and slight increase in activated astrocytes in the OB. In addition, qPCR and ELISA revealed the elevated expression of interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma both in the OB and nasal tissue. Conclusions Taken together, the decreased peripheral OSNs, OB microgliosis, and elevated proinflammatory cytokines suggest that immunological changes in the OB may be involved in the pathogenesis of PVOD.

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Activation of upper respiratory tract mucosal innate immune responses in cats by liposomal toll‐like receptor ligand complexes delivered topically

Journal of Veterinary Internal Medicine ◽

10.1111/jvim.15426 ◽

2019 ◽

Vol 33 (2) ◽

pp. 838-845 ◽

Cited By ~ 2

Author(s):

William Wheat ◽

Lyndah Chow ◽

Jonathan Coy ◽

Elena Contreras ◽

Michael Lappin ◽

...

Keyword(s):

Immune Responses ◽

Respiratory Tract ◽

Innate Immune ◽

Upper Respiratory Tract ◽

Innate Immune Responses ◽

Toll Like Receptor ◽

Receptor Ligand ◽

Upper Respiratory

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The influence of upper respiratory tract inflammation upon tubal function

Clinical Otolaryngology ◽

10.1111/j.1365-2273.1995.tb01851.x ◽

1995 ◽

Vol 20 (3) ◽

pp. 216-218 ◽

Cited By ~ 3

Author(s):

H. TAKAHASHI ◽

A. FUJITA ◽

I. HONJO

Keyword(s):

Respiratory Tract ◽

Upper Respiratory Tract ◽

Tubal Function ◽

Upper Respiratory ◽

Respiratory Tract Inflammation

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Effects of Photochemical Air Pollution and Allergen Exposure on Upper Respiratory Tract Inflammation in Asthmatics

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/ajrccm.156.6.9704127 ◽

1997 ◽

Vol 156 (6) ◽

pp. 1765-1772 ◽

Cited By ~ 33

Author(s):

T. J. N. HILTERMANN ◽

C. R. de BRUIJNE ◽

J. STOLK ◽

A. H. ZWINDERMAN ◽

F. Th. M. SPIEKSMA ◽

...

Keyword(s):

Air Pollution ◽

Respiratory Tract ◽

Allergen Exposure ◽

Upper Respiratory Tract ◽

Upper Respiratory ◽

Respiratory Tract Inflammation

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Nanoparticles from photocopiers induce oxidative stress and upper respiratory tract inflammation in healthy volunteers

Nanotoxicology ◽

10.3109/17435390.2012.691998 ◽

2012 ◽

Vol 7 (5) ◽

pp. 1014-1027 ◽

Cited By ~ 68

Author(s):

Madhu Khatri ◽

Dhimiter Bello ◽

Peter Gaines ◽

John Martin ◽

Anoop K Pal ◽

...

Keyword(s):

Oxidative Stress ◽

Respiratory Tract ◽

Healthy Volunteers ◽

Upper Respiratory Tract ◽

Upper Respiratory ◽

Respiratory Tract Inflammation

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Changes in Circulating Immune Complex and Charge Distribution with Upper Respiratory Tract Inflammation in IgA Nephropathy

Nephron ◽

10.1159/000188507 ◽

1995 ◽

Vol 69 (4) ◽

pp. 384-390 ◽

Cited By ~ 3

Author(s):

Koichi Yamaguchi ◽

Yoshiyuki Ozono ◽

Takashi Harada ◽

Kohei Hara

Keyword(s):

Respiratory Tract ◽

Iga Nephropathy ◽

Charge Distribution ◽

Immune Complex ◽

Upper Respiratory Tract ◽

Circulating Immune Complex ◽

Upper Respiratory ◽

Respiratory Tract Inflammation

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Nasal Tissue Extraction Is Essential for Characterization of the Murine Upper Respiratory Tract Microbiota

mSphere ◽

10.1128/msphere.00562-20 ◽

2020 ◽

Vol 5 (6) ◽

Author(s):

L. Patrick Schenck ◽

Joshua J. C. McGrath ◽

Daphnée Lamarche ◽

Martin R. Stämpfli ◽

Dawn M. E. Bowdish ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Respiratory Tract ◽

Research Design ◽

Respiratory Infections ◽

Upper Respiratory Tract ◽

Content Type ◽

Nasal Tissue ◽

Colonization Success ◽

Upper Respiratory ◽

Nasal Microbiota

ABSTRACT Respiratory infections are a leading cause of morbidity and mortality worldwide. Bacterial pathogens often colonize the upper respiratory tract (nose or mouth) prior to causing lower respiratory infections or invasive disease. Interactions within the upper respiratory tract between colonizing bacteria and the resident microbiota could contribute to colonization success and subsequent transmission. Human carriage studies have identified associations between pathogens such as Streptococcus pneumoniae and members of the resident microbiota, although few mechanisms of competition and cooperation have been identified and would be aided by the use of animal models. Little is known about the composition of the murine nasal microbiota; thus, we set out to improve assessment, including tissue sampling, composition, and comparison between mouse sources. Nasal washes were efficient in sampling the nasopharyngeal space but barely disrupted the nasal turbinates. Nasal tissue extraction increased the yield of cultivable bacterial compared to nasal washes, revealing distinct community compositions. Experimental pneumococcal colonization led to dominance by the colonizing pathogen in the nasopharynx and nasal turbinates, but the composition of the microbiota, and interactions with resident microbes, differed depending on the sampling method. Importantly, vendor source has a large impact on microbial composition. Bacterial interactions, including cooperation and colonization resistance, depend on the biogeography of the nose and should be considered during research design of experimental colonization with pathogens. IMPORTANCE The nasal microbiota is composed of species that play a role in the colonization success of pathogens, including Streptococcus pneumoniae and Staphylococcus aureus. Murine models provide the ability to explore disease pathogenesis, but little is known about the natural murine nasal microbiota. This study established techniques to allow the exploration of the bacterial members of the nasal microbiota. The mouse nasal microbiota included traditional respiratory bacteria, including Streptococcus, Staphylococcus, and Moraxella species. Analyses were affected by different sampling methods as well as the commercial source of the mice, which should be included in future research design of infectious disease research.

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A Clinical Study on the Effect of K-708 (Acemetacin)-A Double Blind Comparative Study with Ibuprofen in Upper Respiratory Tract Inflammation with Fever

Kansenshogaku zasshi ◽

10.11150/kansenshogakuzasshi1970.55.614 ◽

1981 ◽

Vol 55 (9) ◽

pp. 614-629 ◽

Cited By ~ 1

Author(s):

Osamu KITAMOTO ◽

Hiroyuki KOBAYASHI ◽

Masaro KAJI ◽

Seizaburo KASHIWAGI ◽

Kazuo HAYASHIDA ◽

...

Keyword(s):

Clinical Study ◽

Respiratory Tract ◽

Comparative Study ◽

Upper Respiratory Tract ◽

Double Blind ◽

Upper Respiratory ◽

Respiratory Tract Inflammation

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Double Blind Clinical Studies of Fenbufen for Upper Respiratory Tract Inflammation

Practica Oto-Rhino-Laryngologica ◽

10.5631/jibirin.71.45 ◽

1978 ◽

Vol 71 (1) ◽

pp. 45-63

Author(s):

Shuji Sawaki ◽

Toshiki Manabe ◽

Yasushi Ishibashi ◽

Kurata Yuge ◽

Kenichi Nakamura ◽

...

Keyword(s):

Respiratory Tract ◽

Clinical Studies ◽

Upper Respiratory Tract ◽

Double Blind ◽

Upper Respiratory ◽

Respiratory Tract Inflammation

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Retinoic Acid–inducible Gene 1–like Receptors in the Upper Respiratory Tract

American Journal of Rhinology and Allergy ◽

10.2500/ajra.2011.25.3712 ◽

2011 ◽

Vol 25 (6) ◽

pp. e262-e267 ◽

Cited By ~ 3

Author(s):

Jesper Bogefors ◽

Anne Månsson Kvarnhammar ◽

Leith Latif ◽

Terese Petterson ◽

Rolf Uddman ◽

...

Keyword(s):

Retinoic Acid ◽

Respiratory Tract ◽

Nasal Mucosa ◽

Nasal Polyps ◽

Poly I:C ◽

Mrna Levels ◽

Upper Respiratory Tract ◽

Upper Airways ◽

Upper Respiratory ◽

Inducible Gene

Background Retinoic acid–inducible gene 1–like receptors (RLRs) are a novel family of pattern recognition receptors that include retinoic acid–inducible gene 1 (RIG-1), melanoma differentiation-associated gene 5 (MDA-5), and laboratory of genomics and physiology 2 (LGP-2). The knowledge of RLRs and their function in the human airway is limited. This study explores the role of RLRs in the upper respiratory tract. Methods Tonsils, adenoids, nasal polyps, and biopsy specimens from the nasal mucosa were examined for the occurrence of the RIG-1, MDA-5, and LGP-2 using real-time reverse-transcription polymerase chain reaction and immunohistochemistry. The nasopharyngeal epithelial cell line FaDu was cultured with the RIG-1/MDA-5 ligand poly(I:C)/LyoVec (Invivogen, San Diego, CA) and analyzed for cytokine release using ELISA. Results RIG-1, MDA-5, and LGP-2 mRNA were found in all tissues tested. The airway epithelium appeared to be their most prominent location. The RIG-1 and MDA-5 mRNA levels were higher in nasal polyps than in normal nasal mucosa, a state that seemed to be reversed by local steroid treatment. Culture of FaDu with poly(I:C)/LyoVec resulted in IL-6 and IL-8 release. No alteration in RLR expression in tonsils was seen on infection. Conclusion This study shows the presence and functional activity of RLRs in the human upper airways. It also suggests a role for RLRs in nasal polyposis.

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