A Comparative Transcriptome Analysis of Human and Porcine Choroid Plexus Cells in Response to Streptococcus suis Serotype 2 Infection Points to a Role of Hypoxia

Abstract

Streptococcus suis (S. suis) is an important opportunistic pathogen, which can cause septicemia and meningitis in pigs and humans. Previous in vivo observations in S. suis-infected pigs revealed lesions at the choroid plexus (CP). In vitro experiments with primary porcine CP epithelial cells (PCPEC) and human CP epithelial papilloma (HIBCPP) cells demonstrated that S. suis can invade and traverse the CP epithelium, and that the CP contributes to the inflammatory response via cytokine expression. Here, next generation sequencing (RNA-seq) was used to compare global transcriptome profiles of PCPEC and HIBCPP cells challenged with S. suis serotype (ST) 2 infected in vitro, and of pigs infected in vivo. Identified differentially expressed genes (DEGs) were, amongst others, involved in inflammatory responses and hypoxia. The RNA-seq data were validated via quantitative PCR of selected DEGs. Employing Gene Set Enrichment Analysis (GSEA), 18, 28, and 21 enriched hallmark gene sets (GSs) were identified for infected HIBCPP cells, PCPEC, and in the CP of pigs suffering from S. suis ST2 meningitis, respectively, of which eight GSs overlapped between the three different sample sets. The majority of these GSs are involved in cellular signaling and pathways, immune response, and development, including inflammatory response and hypoxia. In contrast, suppressed GSs observed during in vitro and in vivo S. suis ST2 infections included those, which were involved in cellular proliferation and metabolic processes. This study suggests that similar cellular processes occur in infected human and porcine CP epithelial cells, especially in terms of inflammatory response.

Capsule-dependent impact of MAPK signalling on host cell invasion and immune response during infection of the choroid plexus epithelium by Neisseria meningitidis

“…The analysis of GO terms pointed towards an inflammatory response of the HIBCPP cells after infection with Nm , confirming previous transcriptome data of PC epithelial cells in response to bacterial infection [ 3 , 4 , 56 ]. Furthermore, GO terms indicating a negative regulation of apoptosis as well as a cellular response to TNF were detected in all examined conditions.…”

“…The induction of proinflammatory cytokines and chemokines during infection of porcine and human CP cells with bacteria has previously been demonstrated in our laboratory [ 4 , 55 , 56 ]. Here, we applied the MACE RNA-seq technology, which sequences only the 3` end of the transcript and enables sequencing of samples at a deeper level.…”

Editorial: Host-Pathogen Interaction in the Central Nervous System

“…Most of these GSs were reported to be involved in cellular signaling, host immune and inflammatory response (Lauer et al, 2021). This finding clearly suggests that S. suis-infected human and porcine CP epithelial cells share similar cellular processes in the context of host inflammatory response (Lauer et al, 2021).…”

“…Streptococcus suis (S. suis) is an important opportunistic pathogen, which can cause septicemia and meningitis in pigs, but also in humans. In the study by Lauer et al, using Gene Set Enrichment Analysis (GSEA), 18, 28, and 21 enriched hallmark gene sets (GSs) were identified for infected human choroid plexus (CP) epithelial papilloma (HIBCPP) cells, primary porcine CP epithelial cells (PCPEC), and in the CP of pigs affected by S. suis ST2 meningitis, respectively of which 8 GSs overlapped among the three different sample sets (Lauer et al, 2021). Most of these GSs were reported to be involved in cellular signaling, host immune and inflammatory response (Lauer et al, 2021).…”

“…In the study by Lauer et al, using Gene Set Enrichment Analysis (GSEA), 18, 28, and 21 enriched hallmark gene sets (GSs) were identified for infected human choroid plexus (CP) epithelial papilloma (HIBCPP) cells, primary porcine CP epithelial cells (PCPEC), and in the CP of pigs affected by S. suis ST2 meningitis, respectively of which 8 GSs overlapped among the three different sample sets (Lauer et al, 2021). Most of these GSs were reported to be involved in cellular signaling, host immune and inflammatory response (Lauer et al, 2021). This finding clearly suggests that S. suis-infected human and porcine CP epithelial cells share similar cellular processes in the context of host inflammatory response (Lauer et al, 2021).…”