Abstract
Echovirus-30 (E-30) is responsible for the extensive global outbreaks of meningitis in children. To gain access to the central nervous system, E-30 first has to cross the epithelial blood–cerebrospinal fluid barrier. Several meningitis causing bacteria preferentially infect human choroid plexus papilloma (HIBCPP) cells in a polar fashion from the basolateral cell side. Here, we investigated the polar infection of HIBCPP cells with E-30. Both apical and basolateral infections caused a significant decrease in the transepithelial electrical resistance of HIBCPP cells. However, to reach the same impact on the barrier properties, the multiplicity of infection of the apical side had to be higher than that of the basolateral infection. Furthermore, the number of infected cells at respective time-points after basolateral infection was significantly higher compared to apical infection. Cytotoxic effects of E-30 on HIBCPP cells during basolateral infection were observed following prolonged infection and appeared more drastically compared to the apical infection. Gene expression profiles determined by massive analysis of cDNA ends revealed distinct regulation of specific genes depending on the side of HIBCPP cells’ infection. Altogether, our data highlights the polar effects of E-30 infection in a human in vitro model of the blood–cerebrospinal fluid barrier leading to central nervous system inflammation.
Highlights
The entry of various pathogens into the central nervous system (CNS) can lead to meningitis and encephalitis in humans [1,2]
There was no significant decrease in the transepithelial electrical resistance (TEER) following 8 h of infection from the basolateral or the apical side of HIBCPP cells compared to the uninfected control condition, even with a high MOI of 20 (Figure 2A,B)
When HIBCPP cells were apically infected with E-30 for 24 h, only the highest MOI (i.e., 14 and 20) showed a significant TEER decrease compared to the uninfected control condition (p = 0.0044, p = 0.0006, respectively; Figure 2F)
Summary
The entry of various pathogens into the central nervous system (CNS) can lead to meningitis and encephalitis in humans [1,2]. To gain access to the CNS, pathogens need to cross the main barriers, such as the blood–brain barrier (BBB) or the blood–CSF barrier (BCSFB), where they can cause inflammation. It was previously shown in human and porcine in vitro models of the BCSFB that infection with specific bacterial pathogens can alter the properties of the BCSFB and lead to invasion of pathogens into the brain [16,17,18]. Previous publications have shown that the polarity of epithelial cells may be critical for enterovirus infection, such as for Coxsackievirus B3 and Echovirus 7 [21,22]
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