Influenza virus and Staphylococcus aureus super-infection disrupts spatially coordinated cellular immunity in the mouse lung
Year: 2025
Type: article
Abstract: Influenza-associated bacterial super-infections in the lung lead to increased morbidity and mortality. Previous studies have investigated how preceding viral infection causes dysregulation of the innate and adaptive immune systems, leading to increased susceptibility of developing secondary bacterial pneumonia. However, these previous studies cannot account for the spatial context of immune cells in lung. In our study, we employ a spatial transcriptomics platform (10X Genomics Visium) to systematically characterize the coordination of immune cells during super-infection. We compare deconvoluted spatial transcriptomics data between super-infection and single influenza and methicillin-resistant Staphylococcus aureus infections. Consequently, we find that the recruitment of neutrophils and interstitial macrophages from lung parenchyma to the airways is inhibited in super-infection, likely impairing pathogen clearance. Additionally, by analyzing cell colocalization and signaling, we find that the interaction between CD4+ T cells, B cells, and dendritic cells is disrupted by secondary bacterial super-infection. These findings are confirmed by immunofluorescence staining. Our study constructs a spatial sequencing atlas of lung super-infection, highlighting how secondary bacterial challenge significantly impacts recruitment and signaling of immune cells. These findings provide insight into the aberrant inflammation in the super-infected lung and may aid development of therapeutics that target key immune cell recruitment pathways. The authors report a spatial transcriptomic analysis of mouse lungs following a super-infection of influenza and methicillin-resistant Staphylococcus aureus.
Source: Communications Biology
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: U.S. Department of Health and Human Services, University of Pittsburgh, National Institutes of Health, Center for Research Computing, University of Pittsburgh, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, Children's Hospital of Pittsburgh
Awards: G1381518247, G1786722461, Immune Airway-Epithelial Interactions in Steroid-Refractory Severe Asthma, G2301599484, Influenza A Inhibits TH17 Host Defense Against Bacterial Pneumonia, G2592393619, G265994000, G3025648356, G3274338153, G366700239, The Role of Staphylococcus aureus SasD in Lung, G4111292945, High-Throughput Computing for Genomics and Bioinformatics Research, G5168452182, G642779400, G6704094629, G6919064462, G69737326, G7080873127, Immunology of Infectious Disease, G9000000100, G9000119838, G9000120822, G9000153736, G9000178867, G9000237563
OpenAlex ID: W4416553057