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Microbiota of the Respiratory Tract

Microbiota of the Respiratory Tract

The human respiratory tract, comprising the upper and lower segments, serves as a critical interface with the external environment. The upper respiratory tract (URT)—including the nostrils, sinuses, pharynx, and oropharynx—is heavily colonized by microbes, while the lower respiratory tract (LRT), composed of the larynx, trachea, bronchi, and lungs, was long thought to be sterile. However, recent molecular studies have revealed that the lungs are not devoid of microbes but act more...

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Intra-tracheal Administration of Haemophilus influenzae in Mouse Models to Study Airway Inflammation

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Upper Respiratory Tract OC43 Infection Model for Investigating Airway Immune-Modifying Therapies.

Jason L N Girkin¹, Nathan E Bryant¹, Su-Ling Loo¹

¹Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.

American Journal of Respiratory Cell and Molecular Biology

|August 21, 2023

Summary

A mouse model using human coronavirus OC43 in the upper respiratory tract (URT) effectively demonstrates nasal antiviral immunity. Treatments targeting Toll-like receptor 2 (TLR2) show promise for managing URT infections.

Keywords:

OC43 TLR2 coronavirus innate immunity mouse model

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Published on: May 10, 2022

Area of Science:

Immunology
Virology
Respiratory Medicine

Background:

Upper respiratory tract (URT) infections, including those caused by coronaviruses like OC43, are significant public health concerns.
Effective antiviral immune responses in the nasal mucosa are crucial for preventing severe disease and transmission.
The lack of suitable URT infection models hinders the development of nasal treatments for coronavirus immunity.

Purpose of the Study:

To establish and validate a mouse model of OC43 infection in the URT.
To assess the efficacy of nasal-targeting immune-modifying treatments in this model.
To investigate the role of Toll-like receptor 2 (TLR2) in beta-coronavirus innate immunity.

Main Methods:

Intranasal inoculation of OC43 in wild-type Balb/c mice.
Assessment of viral tropism and replication in the respiratory tract.
Quantification of antiviral cytokines (e.g., IFN-λ) and gene expression analysis.
Evaluation of immune-modulating therapies: TLR2/6 agonist (INNA-X) and corticosteroid (fluticasone propionate).

Main Results:

OC43 productively replicated in the mouse nasal epithelium, with peak viral RNA at 2 days post-infection.
Prophylactic INNA-X treatment enhanced virus-induced IFN-λ and IFN-stimulated gene expression.
Intranasal fluticasone propionate increased viral load and suppressed IFN responses, an effect partially mitigated by prior INNA-X treatment.

Conclusions:

The mouse nasal epithelium is susceptible to OC43 infection, establishing a relevant model for URT coronavirus studies.
TLR2 activation is a key determinant of innate antiviral immunity against beta-coronaviruses.
Nasal immune-modulating therapies, particularly TLR2 agonists, hold therapeutic potential for URT coronavirus infections.