Influenza A virus infection induces initial proliferation of commensal Streptococcus pneumoniae in the larynx leading to dissemination into the lower respiratory tract
Year: 2026
Type: article
Abstract: ABSTRACT Secondary bacterial pneumonia is a major complication of influenza A virus (IAV) infection, frequently caused by Streptococcus pneumoniae . Pneumococci asymptomatically colonize the upper respiratory tract by forming biofilms. Viral infections, such as IAV, disrupt this stable colonization, leading to bacterial migration to the lower respiratory tract, and the development of severe pneumonia. However, the specific organs and tissues where IAV infection enhances the replication capacity of pneumococci in the biofilm state remain unclear. In this study, we engineered a mutant S. pneumoniae strain carrying the near-infrared luciferase gene, Akaluc , which is selectively expressed during the log phase. Using this strain, we established a mouse model that enables in vivo imaging of pneumococcal activation following IAV infection. In this model, IAV infection resulted in a marked increase in luminescence signals in the larynx, accompanied by increased bacterial proliferation in the lower respiratory tract. These results suggest that the larynx serves as a key site for pneumococcal activation and transition from biofilm to planktonic state during secondary bacterial pneumonia. Our imaging approach offers a powerful tool for elucidating host-pathogen interactions in vivo and may contribute to the development of preventive strategies against secondary bacterial pneumonia following IAV infection. IMPORTANCE Seasonal influenza virus infection increases the risk of severe bacterial pneumonia, but the underlying mechanisms remain unclear. In this study, we used a mouse model and a pneumococcal mutant strain expressing a near-infrared luminescent protein in the log phase, enabling in vivo monitoring of the enhanced replication of pneumococci in deep tissues. We discovered that following influenza virus infection, bacterial replication is predominantly activated in the larynx, indicating that the larynx serves as a key site for activation of commensal pneumococci. This insight may inform the development of better strategies to prevent secondary bacterial pneumonia.
Source: Journal of Virology
DOI: 10.1128/jvi.00555-26
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Funders: Takeda Science Foundation, Japan Agency for Medical Research and Development, Research Promotion Foundation, Shionogi, University of Tsukuba, Japan Society for the Promotion of Science, Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Co-creation place formation support program, Shionogi Infectious Disease Research Promotion Foundation
Awards: G1753308981, G2605446147, G2733961468, G3577105562, 新興インフルエンザの出現予測を可能にする分子基盤の開発, G4741726089, G4753325450, G5482270805, ウイルス感染病態を決定する炎症性臓器環境の形成原理の解明, つくば型デジタルバイオエコノミー社会形成の国際拠点, G6788436504, G7374233449, Development of Cell Therapy for Secondary Bacterial Pneumonia Using Macrophages with Stable Expression of Phagocytic Receptors
OpenAlex ID: W7166507655
