Streptococcus pneumoniae Infection of Host Epithelial Cells via Polymeric Immunoglobulin Receptor Transiently Induces Calcium Release from Intracellular Stores

Abstract

The pneumococcal surface protein C (PspC) is a major adhesin of Streptococcus pneumoniae (pneumococci) that interacts in a human-specific manner with the ectodomain of the human polymeric immunoglobulin receptor

Endocytosis of Streptococcus pneumoniae via the polymeric immunoglobulin receptor of epithelial cells relies on clathrin and caveolin dependent mechanisms

“…Remarkably, pneumococci were also able to persist in lysosomes up to 4 h after internalization (Fig. S1), an observation that is in agreement to our previous results (Asmat et al, 2011). Although pneumococci may persist for longer periods in lysosomes and are able to exit phagosomes (Noske et al, 2009), which consequently leads to transcytosis (Ring et al, 1998), the majority of intracellular pneumococci are most likely killed when the pIgR route is exploited.…”

“…In contrast, wild-type lactococci were not internalized and hence, did not co-localize with Lamp1 ( Fig. 1), which is in agreement to our previous studies (Asmat et al, 2011;Asmat et al, 2012). These results demonstrated that the PspC-pIgR interaction is a key route for pneumococcal endocytosis by epithelial cells and suggested the intracellular trafficking of pneumococci from early endosomes to late endosomal compartments or phagolysosomes.…”

“…S1). However, as demonstrated earlier the proportion of viable pneumococci decreases dramatically after prolonged infection periods as quantified in antibiotic protection assays (Agarwal et al, 2013;Asmat et al, 2011). Importantly, recombinant lactococci expressing a PspC as their sole adhesin (Asmat et al, 2012), were also taken up by pIgR-expressing Calu-3 and MDCKhpIgR cells starting already 30 min post-infection and maintaining entrapped in phagolysosomes for up to 150 min and 240 min postinfection ( Fig.…”

“…Infection studies using epithelial or endothelial cells further demonstrated that the major proportion of intracellular pneumococci is time-dependently killed (Asmat et al, 2011;Zhang et al, 2000). Killing of pneumococci by primary human dendritic cells was associated with their localization in phagolysosomes (Noske et al, 2009).…”

“…Recently we have demonstrated that PspC-pIgR mediated pneumococcal uptake by host epithelial cells is a highly complex process and involves a concerted role of host cell cytoskeleton and signalling pathways ). These include the activity of small GTPase member Cdc42, phosphatidylinositol 3-kinase (PI3K), Akt and transient release of calcium from intracellular stores (Agarwal et al, 2010a;Asmat et al, 2011). In addition, PspC-pIgR -mediated internalization of pneumococci requires a co-ordinated signalling of Src PTKs, FAK, ERK1/2, and JNK (Agarwal et al, 2010a).…”