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Updated: Jun 16, 2025
Generation, Amplification, and Titration of Recombinant Respiratory Syncytial Viruses
Published on: April 4, 2019
RSV enhances Staphylococcus aureus bacterial growth in the lung
Helen E Rich1, Simran Bhutia1, Francina Gonzales de Los Santos1
1Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
Abstract:
Patients coinfected with respiratory syncytial virus (RSV) and bacteria have longer hospital stays, higher risk of intensive care unit admission, and worse outcomes. We describe a model of RSV line 19F/methicillin-resistant Staphylococcus aureus (MRSA) USA300 coinfection that does not impair viral clearance, but prior RSV infection enhances USA300 MRSA bacterial growth in the lung. The increased bacterial burden post-RSV correlates with reduced accumulation of neutrophils and impaired bacterial killing by alveolar macrophages. Surprisingly, reduced neutrophil accumulation is likely not explained by reductions in phagocyte-recruiting chemokines or alterations in proinflammatory cytokine production compared with mice infected with S. aureus alone. Neutrophils from RSV-infected mice retain their ability to migrate toward chemokine signals, and neutrophils from the RSV-infected lung are better able to phagocytize and kill S. aureus ex vivo on a per cell basis. In contrast, while alveolar macrophages could ingest USA300 post-RSV, intracellular bacterial killing was impaired. The RSV/S. aureus coinfected lung promotes a state of overactivation in neutrophils, demonstrated by increased production of reactive oxygen species (ROS) that can drive formation of neutrophil extracellular traps (NETs), resulting in cell death. Mice with RSV/S. aureus coinfection had increased extracellular DNA and protein in bronchoalveolar lavage fluid and histological evidence confirmed NETosis in vivo. Taken together, these data highlight that prior RSV infection can prime the overactivation of neutrophils leading to cell death that impairs neutrophil accumulation in the lung. Additionally, alveolar macrophage killing of bacteria is impaired post-RSV. Together, these defects enhance USA300 MRSA bacterial growth in the lung post-RSV.
Insights
Prior respiratory syncytial virus (RSV) infection impairs lung immune defenses, leading to enhanced growth of Staphylococcus aureus (MRSA) and worse patient outcomes. This occurs due to neutrophil overactivation and impaired macrophage bacterial killing.
Area of Science:
- Immunology
- Microbiology
- Pulmonology
Background:
- Coinfection with respiratory syncytial virus (RSV) and bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), is associated with severe patient outcomes, including prolonged hospitalization and increased ICU admission.
- Understanding the immunological mechanisms underlying RSV and bacterial coinfection is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the impact of prior respiratory syncytial virus (RSV) infection on the host immune response to subsequent methicillin-resistant Staphylococcus aureus (MRSA) USA300 lung infection.
- To elucidate the cellular and molecular mechanisms driving enhanced bacterial growth in the context of RSV-MRSA coinfection.
Main Methods:
- Establishment of a murine model of sequential RSV and MRSA USA300 coinfection.
- Assessment of viral clearance, bacterial burden, neutrophil and alveolar macrophage function (phagocytosis, bacterial killing, reactive oxygen species production).
- Analysis of bronchoalveolar lavage fluid for extracellular DNA and protein, and histological examination for neutrophil extracellular trap formation (NETosis).
Main Results:
- Prior RSV infection did not impede viral clearance but significantly enhanced MRSA USA300 bacterial growth in the lung.
- RSV coinfection led to impaired neutrophil accumulation and reduced bacterial killing by alveolar macrophages.
- Neutrophils exhibited signs of overactivation, increased reactive oxygen species production, and NETosis, resulting in cell death and impaired bacterial clearance.
Conclusions:
- Prior RSV infection primes neutrophils towards overactivation and cell death, compromising their accumulation and function in the lung.
- Alveolar macrophage-mediated bacterial killing is impaired following RSV infection.
- These combined immune defects contribute to enhanced MRSA USA300 growth in the lung during RSV coinfection, highlighting a critical interplay between viral and bacterial pathogens.
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