Neutrophils are needed for an effective immune response against pulmonary rat coronavirus infection, but also contribute to pathology

Area of Science:

• Immunology
• Virology
• Pathology

Background:

• Polymorphonuclear neutrophils (PMN) are key immune cells infiltrating the respiratory tract during viral infections.
• Coronaviruses cause a spectrum of respiratory illnesses, with severity varying by strain.
• The role of PMN in coronavirus-induced lung disease, particularly in the natural host, requires further elucidation.

Purpose of the Study:

• To investigate the dual role of PMN in host defense and lung pathology during rat coronavirus (RCoV) infection in its natural host.
• To analyze the impact of PMN depletion on disease progression, viral replication, and inflammatory responses in RCoV-infected rats.

Main Methods:

• PMN were depleted in adult rats naturally infected with RCoV.
• Disease progression, including weight loss, clinical signs, mortality, and viral replication, was monitored.
• Inflammatory responses, lung pathology, and immune cell infiltration (macrophages, lymphocytes) were analyzed.
• In vitro experiments assessed PMN cytokine and chemokine production in response to RCoV-infected cells.

Main Results:

• PMN depletion exacerbated RCoV disease, leading to increased weight loss, clinical signs, mortality, and prolonged viral replication.
• Depleted animals showed reduced infiltration of macrophages and lymphocytes in the respiratory tract and lower chemokine levels.
• In vitro studies confirmed that PMN produce cytokines and chemokines upon encountering RCoV-infected alveolar epithelial cells.
• Despite their protective role, PMN presence correlated with lung hemorrhage, increased epithelial permeability, and inflammation.

Conclusions:

• PMN are essential for an effective antiviral response against RCoV, protecting against severe disease.
• PMN also contribute to lung inflammation and pathology during RCoV infection, highlighting a complex, dual role.
• Understanding this balance is critical for managing coronavirus-induced respiratory diseases.