Abstract
Studies have shown that exposure to environmental tobacco smoke can increase the risk of bacterial meningitis, and nicotine is the core component of environmental tobacco smoke. Autophagy is an important way for host cells to eliminate invasive pathogens and resist infection. Escherichia coli K1 strain (E. coli K1) is the most common Gram-negative bacterial pathogen that causes neonatal meningitis. The mechanism of nicotine promoting E. coli K1 to invade human brain microvascular endothelial cells (HBMECs), the main component of the blood–brain barrier, is not clear yet. Our study found that the increase of HBMEC autophagy level during E. coli K1 infection could decrease the survival of intracellular bacteria, while nicotine exposure could inhibit the HBMEC autophagic response of E. coli K1 infection by activating the NF-kappa B and PI3K/Akt/mTOR pathway. We concluded that nicotine could inhibit HBMEC autophagy upon E. coli K1 infection and decrease the scavenging effect on E. coli K1, thus promoting the occurrence and development of neonatal meningitis.
Highlights
Neonatal bacterial meningitis (NBM) is a serious life-threatening infectious disease of the central nervous system (Heckenberg et al, 2014; Iovino et al, 2014)
High level of bacteremia is a necessary condition for meningitis (Doran et al, 2016; Kim, 2016), and nicotine (NT), the main component of tobacco smoke, can significantly enhance the invasion of human brain microvascular endothelial cells (HBMECs), which are the main component of the blood–brain barrier (Wang et al, 2003)
To investigate autophagy level of HBMECs in the context of E. coli K1 infection, HBMECs were infected with E. coli strain E44 for different amounts of time, and the results showed the expression of LC3II in E44-infected HBMECs in a time-dependent manner, with peak conversion at 2 h (Supplementary Figure 1)
Summary
Neonatal bacterial meningitis (NBM) is a serious life-threatening infectious disease of the central nervous system (Heckenberg et al, 2014; Iovino et al, 2014). In E. coli meningitis, α7 nAChR is critical for the activation of the NF-κB signaling pathway in HBMECs (Chen et al, 2002; Chi et al, 2011a). The continuous activation of NF-κB signaling pathway can negatively or positively regulate autophagy; it is unclear whether activation of the NF-κB signaling pathway regulates autophagy in HBMECs infected with E. coli K1 ADDIN EN.CITE (Koedel et al, 2000; Vallabhapurapu and Karin, 2009). The activation of mTOR can inhibit autophagy, and it was regulated by multiple upstream signals, PI3K/Akt is one of the most important regulatory signal pathways (Deretic et al, 2013). Whether the NT can regulate the autophagy of E. coli K1–infected HBMECs through PI3K/Akt/mTOR pathway needs us to further explore
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
