Capillary leakage provides nutrients and antioxidants for rapid pneumococcal proliferation in influenza-infected lower airways
Vicky Sender, Karina Hentrich, Anuj Pathak, Alicia Qian Ler Tan, Bethel Tesfai Embaie, Susanna L. Lundström, Massimiliano Gaetani, Jan Bergstrand, Rei Nakamoto, Lok‐To Sham, Jerker Widengren, Staffan Normark, Birgitta Henriques‐Normark
Abstract
Influenza A virus (IAV)-related mortality is often due to secondary bacterial infections, primarily by pneumococci. Here, we study how IAV-modulated changes in the lungs affect bacterial replication in the lower respiratory tract (LRT). Bronchoalveolar lavages (BALs) from coinfected mice showed rapid bacterial proliferation 4 to 6 h after pneumococcal challenge. Metabolomic and quantitative proteomic analyses demonstrated capillary leakage with efflux of nutrients and antioxidants into the alveolar space. Pneumococcal adaptation to IAV-induced inflammation and redox imbalance increased the expression of the pneumococcal chaperone/protease HtrA. Presence of HtrA resulted in bacterial growth advantage in the IAV-infected LRT and protection from complement-mediated opsonophagocytosis due to capsular production. Absence of HtrA led to growth arrest in vitro that was partially restored by antioxidants. Pneumococcal ability to grow in the IAV-infected LRT depends on the nutrient-rich milieu with increased levels of antioxidants such as ascorbic acid and its ability to adapt to and cope with oxidative damage and immune clearance.