Inhibition of the PI3K/AKT Signaling Pathway or Overexpression of Beclin1 Blocks Reinfection of Streptococcus pneumoniae After Infection of Influenza A Virus in Severe Community-Acquired Pneumonia

Abstract

Streptococcus pneumoniae (S. pneumoniae) and viruses are considered as primary risks of community-acquired pneumonia (CAP), and the effects of co-infection bacterial and virus in the prognosis of patients with severe CAP (SCAP) are poorly described. Therefore, this study is conducted to investigate the regulation of Beclin1-PI3K/AKT axis in reinfection of S. pneumoniae after influenza A virus in mice model of bronchoalveolar lavage fluid (BALF). Samples of sputum and BALF were collected from patients with SCAP for etiological detection. The expression of each gene was determined by RT-qPCR and western blot analysis. Influenza A/PR/8/34 and S. pneumoniae were used to establish the mice model of reinfection pneumonia. The virus quantity, expression levels of inflammatory factors, bacterial load, and myeloperoxidase (MPO) activity were tested. HE staining was applied to observe histopathology of lung tissue. The expression of Beclin1 was downregulated and the PI3K/AKT pathway was activated in viral pneumonia. In vivo experiment, the reinfection of S. pneumoniae following influenza A virus infection increased the number of S. pneumoniae population, the activity of MPO, and the expression of TNF-α, IL-6, and IFN-γ in BALF of mice. In contrast, inhibition of the PI3K/AKT pathway or overexpression of Beclin1 reduced the number of S. pneumoniae population, the activity of MPO, and the expression of TNF-α, IL-6, and IFN-γ in BALF of mice reinfected with S. pneumoniae after influenza A virus infection. Collectively, our study demonstrates that inhibition of the PI3K/AKT signaling pathway or overexpressed Beclin1 alleviates reinfection of S. pneumoniae after influenza A virus infection in SCAP.

MicroRNA‑4485 ameliorates severe influenza pneumonia via inhibition of the STAT3/PI3K/AKT signaling pathway

“…Streptococcus pneumonia induces autophagy in A549 cells via a PI3K/AKT/mTOR-dependent mechanism ( 26 ). Yang et al ( 27 ) demonstrated that inhibition of PI3K/AKT/mTOR decreases the reinfection of Streptococcus pneumonia following influenza A virus infection in community-acquired pneumonia. Therefore, the present study aimed to explore whether the effects of miR-4485 on H1N1-induced severe pneumonia could be mediated via the PI3K/AKT/mTOR signaling pathway.…”

Shen-ling-bai-zhu-san ameliorates inflammation and lung injury by increasing the gut microbiota in the murine model of Streptococcus pneumonia-induced pneumonia

“…After the 14-day treatment, mice were anesthetized with 3% pentobarbital sodium (P3761; Sigma-Aldrich, St Louis, MO, USA), and the broncho-alveolar lavage fluid (BALF) of the mice in each group was obtained by intratracheal lavage, as previously described [22]. The collected BALF (0.8 mL) was then centrifuged at 4°C for 10 min at 260×g, and the precipitate re-suspended in 0.5 mL sterile PBS.…”

Integration of Ni/NiO nanoparticles and a microfluidic ELISA chip to generate a sensing platform for Streptococcus pneumoniae detection

“…19 This method is extensively used to detect biological material; however, the technical limitations of ELISA include the requirement of a liquid system and long reaction time, which thereby limits the scope for method enhancement. [20][21][22] In this study, a magnetic microuidic ELISA system (MMF-ELISA) was designed to allow for rapid ELISA systems (Fig. 1).…”