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Updated: Jan 10, 2026
Using Bioluminescent Imaging to Investigate Synergism Between Streptococcus pneumoniae and Influenza A Virus in Infant Mice
Published on: April 14, 2011
Influenza virus and Staphylococcus aureus super-infection disrupts spatially coordinated cellular immunity in the
Tianhao Liu1,2, Leigh M Miller1, Brooke P Dresden1
1Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
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.
Insights
Bacterial super-infections after influenza impair immune cell movement and communication in the lung. This spatial analysis reveals disrupted immune cell coordination, impacting pathogen clearance and inflammation during secondary bacterial pneumonia.
Area of Science:
- Pulmonary immunology
- Infectious disease pathology
- Spatial transcriptomics
Background:
- Influenza-associated bacterial super-infections increase lung morbidity and mortality.
- Previous research explored immune system dysregulation but lacked spatial context.
- Understanding immune cell spatial coordination is crucial for super-infection.
Purpose of the Study:
- To characterize immune cell coordination during lung super-infection using spatial transcriptomics.
- To compare spatial immune cell responses in super-infection versus single infections.
- To identify spatial disruptions impacting pathogen clearance and immune signaling.
Main Methods:
- Utilized 10X Genomics Visium spatial transcriptomics platform.
- Compared deconvoluted data from super-infection, influenza, and Staphylococcus aureus models.
- Analyzed cell colocalization, signaling pathways, and confirmed with immunofluorescence staining.
Main Results:
- Super-infection inhibited neutrophil and interstitial macrophage recruitment to airways.
- Impaired recruitment likely hinders pathogen clearance in super-infected lungs.
- Disrupted interactions were observed between CD4+ T cells, B cells, and dendritic cells.
Conclusions:
- Constructed a spatial atlas of lung super-infection revealing immune cell recruitment and signaling impacts.
- Secondary bacterial challenge significantly alters immune cell spatial coordination.
- Findings offer insights into aberrant lung inflammation and potential therapeutic targets.
