Molecular basis of early epithelial response to streptococcal exotoxin: role of STIM1 and Orai1 proteins: Streptolysin O activates SOC entry

Usmani, Shariq M.; von Einem, Jens; Frick, Manfred; Miklavc, Pika; Mayenburg, Martina; Husmann, Matthias; Dietl, Paul; Wittekindt, Oliver H.

Abstract

Streptolysin O (SLO) is a cholesterol-dependent cytolysin (CDC) from Streptococcus pyogenes. SLO induces diverse types of Ca2+ signalling in host cells which play a key role in membrane repair and cell fate determination. The mechanisms behind SLO-induced Ca2+ signalling remain poorly understood. Here, we show that in NCI-H441 cells, wild-type SLO as well as non-pore-forming mutant induces long-lasting intracellular Ca2+ oscillations via IP3-mediated depletion of intracellular stores and activation of store-operated Ca2+ (SOC) entry. SLO-induced activation of SOC entry was confirmed by Ca2+ add-back experiments, pharmacologically and by overexpression as well as silencing of STIM1 and Orai1 expression. SLO also activated SOC entry in primary cultivated alveolar type II (ATII) cells but Ca2+ oscillations were comparatively short-lived in nature. Comparison of STIM1 and Orai1 revealed a differential expression pattern in H441 and ATII cells. Overexpression of STIM1 and Orai1 proteins in ATII cells changed the short-lived oscillatory response into a long-lived one. Thus, we conclude that SLO-mediated Ca2+ signalling involves Ca2+ release from intracellular stores and STIM1/Orai1-dependent SOC entry. The phenotype of Ca2+ signalling depends on STIM1 and Orai1 expression levels. Our findings suggest a new role for SOC entry-associated proteins in S. pyogenes-induced lung infection and pneumonia.

Citation

Usmani, S. M., von Einem, J., Frick, M., Miklavc, P., Mayenburg, M., Husmann, M., …Wittekindt, O. H. (2012). Molecular basis of early epithelial response to streptococcal exotoxin: role of STIM1 and Orai1 proteins: Streptolysin O activates SOC entry. Cellular Microbiology, 14(3), 299-315. https://doi.org/10.1111/j.1462-5822.2011.01724.x

• Journal Article Type: Article
• Online Publication Date: Dec 13, 2011
• Publication Date: 2012-03
• Deposit Date: Mar 4, 2024
• Journal: Cellular Microbiology
• Print ISSN: 1462-5814
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 3
• Pages: 299-315
• DOI: https://doi.org/10.1111/j.1462-5822.2011.01724.x
• Keywords: Virology; Immunology; Microbiology