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Alveolar Macrophage Phagocytosis and Bacteria Clearance in Mice
Published on: March 2, 2019
Alveolar macrophages protect mice from MERS-CoV-induced pneumonia and severe disease
Rudragouda Channappanavar1, Muneeswaran Selvaraj1, Sunil More1
1Oklahoma State University, Stillwater, OK.
Abstract:
Emerging and re-emerging human coronaviruses (hCoVs) cause severe respiratory illness in humans, but the basis for lethal pneumonia in these diseases is not well understood. Alveolar macrophages (AMs) are key orchestrators of host antiviral defense and tissue tolerance during a variety of respiratory infections, and AM dysfunction is associated with severe COVID-19. In this study, using a mouse model of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, we examined the role of AMs in MERS pathogenesis. Our results show that depletion of AMs using clodronate (CL) liposomes significantly increased morbidity and mortality in human dipeptidyl peptidase 4 knock-in (hDPP4-KI) mice. Detailed examination of control and AM-depleted lungs at different days postinfection revealed increased neutrophil activity but a significantly reduced MERS-CoV-specific CD4 T-cell response in AM-deficient lungs during later stages of infection. Furthermore, enhanced MERS severity in AM-depleted mice correlated with lung inflammation and lesions. Collectively, these data demonstrate that AMs are critical for the development of an optimal virus-specific T-cell response and controlling excessive inflammation during MERS-CoV infection.
Insights
Alveolar macrophages (AMs) are crucial for controlling Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Their depletion worsens MERS-CoV disease by impairing T-cell responses and increasing lung inflammation.
Area of Science:
- Immunology
- Virology
- Pathogenesis
Background:
- Human coronaviruses (hCoVs) cause severe respiratory illness, with lethal pneumonia mechanisms unclear.
- Alveolar macrophages (AMs) are vital for antiviral defense and tissue tolerance in respiratory infections.
- AM dysfunction is linked to severe COVID-19, suggesting a role in other hCoV diseases.
Purpose of the Study:
- To investigate the role of AMs in Middle East respiratory syndrome coronavirus (MERS-CoV) pathogenesis.
- To understand how AMs influence host defense and disease severity during MERS-CoV infection.
Main Methods:
- Used a mouse model of MERS-CoV infection with human dipeptidyl peptidase 4 (hDPP4-KI) mice.
- Depleted AMs using clodronate (CL) liposomes to assess their impact on MERS-CoV pathogenesis.
- Analyzed lung tissues for immune cell activity (neutrophils, CD4 T-cells), inflammation, and lesions.
Main Results:
- AM depletion significantly increased morbidity and mortality in MERS-CoV infected hDPP4-KI mice.
- AM-deficient lungs showed increased neutrophil activity but a reduced MERS-CoV-specific CD4 T-cell response.
- Enhanced MERS severity in AM-depleted mice correlated with increased lung inflammation and lesions.
Conclusions:
- Alveolar macrophages are critical for mounting an effective virus-specific T-cell response during MERS-CoV infection.
- AMs play a key role in controlling excessive inflammation and limiting lung pathology in MERS-CoV infection.
- These findings highlight AMs as important targets for therapeutic strategies against severe coronavirus respiratory diseases.
