UTMB Health SHARED
UTMB Health SHARED is an online community space for Scholarship, Historical Archives, Repository, & Electronic Dissertations. This digital service is an important tool for preserving the organization’s legacy and facilitating scholarly communication.
Communities in UTMB Health SHARED
Select a community to browse its collections.
- Completed capstone projects from students of the School of Health Professions
- Publications by degree candidates from the Graduate School of Biomedical Sciences, the School of Nursing, and the School of Public and Population Health
- Profiles of UTMB faculty and staff, including selected works.
- Historical images and documents from Moody Medical Library special collections
- Public documents produced by university departments
Recent Submissions
Oak Park Hospital
(C.R. Childs, Company, Chicago, 1941-10-25)
Postcard of the Oak Park Hospital in Oak Park, Illinois.
Greater West Suburban Hospital
(Curt Teich & Company., Inc., Chicago, Unknown)
Postcard of the Greater West Suburban Hospital in Oak Park, Illinois.
The Balance of Interferon-γ and Interleukin-10 during Influenza A Virus Infection Complicated by Methicillin-Resistant Staphylococcus aureus Superinfection
(2024-12) McKelvey, Michael Daniel 1997-; Sun, Keer (kesun@utmb.edu); Chopra, Ashok (achopra@utmb.edu); Huber, Victor (Victor.Huber@usd.edu); Soong, Lynn (Lysoong@utmb.edu); Walker, David (dwalker@utmb.edu)
Immune activation is necessary to mount a protective immune response against viral and bacterial infections, but an overzealous response can lead to the development of acute respiratory distress syndrome (ARDS). ARDS is a highly lethal inflammatory lung injury that is associated with dysregulated cytokine production and decreased lung compliance. No specific treatment exists for ARDS due to the limited understanding of its pathogenesis. We have developed an influenza A virus (IAV) and methicillin-resistant Staphylococcus aureus (MRSA) superinfection model with antibiotic therapy that resembles severe secondary bacterial pneumonia in patients that often progresses to ARDS. Despite antibiotic therapy, mice still succumb to superinfection-induced inflammatory lung damage. Using single-cell RNA sequencing, we reveal significant transcriptome alterations prompted by interferon (IFN)-γ. Transgenic mouse studies demonstrate that IFN-γ receptor (IFN-γR) signaling in mononuclear phagocytes induces tumor necrosis factor (TNF)-α hyperproduction and lethal inflammatory lung damage, with no detectable benefit to viral or bacterial clearance. In contrast, we show that interleukin (IL)-10 is crucial to counteract the lethal IFN-γ-induced cytokine storm and preserve lung function. Transgenic mice with ablation of the IL-10 receptor α gene in mononuclear phagocytes have significantly higher levels of IFN-γ and TNF-α, and a higher mortality rate. This reveals the importance of mononuclear phagocytes in shifting the balance between immunopathology and protective immunity. By omitting antibiotic therapy from the superinfection model, we show that IL-10 also impairs bacterial clearance, specifically when the IL-10Rα gene is ablated in interferon-I-responsive monocytes. Collectively, this body of evidence demonstrates the dominant role played by hypercytokinemia and acute lung damage during post-influenza bacterial pneumonia and the balance of IFN-γ and IL-10 that shifts the balance between immunopathogenesis and bacterial outgrowth.