Rhinovirus-induced calcium flux triggers NLRP3 and NLRC5 activation in bronchial cells

Kathy Triantafilou; Satwik Kar; Frank J M van Kuppeveld; Martha Triantafilou

doi:10.1165/rcmb.2013-0032OC

Rhinovirus-induced calcium flux triggers NLRP3 and NLRC5 activation in bronchial cells

Am J Respir Cell Mol Biol. 2013 Dec;49(6):923-34. doi: 10.1165/rcmb.2013-0032OC.

Authors

Kathy Triantafilou¹, Satwik Kar, Frank J M van Kuppeveld, Martha Triantafilou

Affiliation

¹ 1 Cardiff University, Institute of Infection and Immunity, Department of Child Health, School of Medicine, University Hospital of Wales, Heath Park, Cardiff, Wales; and.

PMID: 23815151
DOI: 10.1165/rcmb.2013-0032OC

Abstract

Human rhinoviruses have been linked with underlying lung disorders, such as asthma and chronic obstructive pulmonary disease, in children and adults. However, the mechanism of virus-induced airway inflammation is poorly understood. In this study, using virus deletion mutants and silencing for nucleotide-binding oligomerization domain-like receptors (NLRs), we show that the rhinovirus ion channel protein 2B triggers NLRP3 and NLRC5 inflammasome activation and IL-1β secretion in bronchial cells. 2B protein targets the endoplasmic reticulum and Golgi and induces Ca(2+) reduction in these organelles, thereby disturbing the intracellular calcium homeostasis. NLRP3 and NLRC5 act in a cooperative manner during the inflammasome assembly by sensing intracellular Ca(2+) fluxes and trigger IL-1β secretion. These results reveal for the first time that human rhinovirus infection in primary bronchial cells triggers inflammasome activation.

MeSH terms

Asthma / etiology
Asthma / metabolism
Asthma / virology
Bronchi / metabolism*
Bronchi / virology*
Calcium Signaling / physiology*
Carrier Proteins / antagonists & inhibitors
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Cells, Cultured
Endoplasmic Reticulum / metabolism
Endoplasmic Reticulum / virology
Gene Knockdown Techniques
Golgi Apparatus / metabolism
Golgi Apparatus / virology
Humans
Inflammasomes / metabolism
Interleukin-1beta / biosynthesis
Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism*
NLR Family, Pyrin Domain-Containing 3 Protein
Picornaviridae Infections / complications
Picornaviridae Infections / metabolism
Picornaviridae Infections / virology
Pulmonary Disease, Chronic Obstructive / etiology
Pulmonary Disease, Chronic Obstructive / metabolism
Pulmonary Disease, Chronic Obstructive / virology
Rhinovirus / genetics
Rhinovirus / metabolism
Rhinovirus / pathogenicity*
Viral Proteins / metabolism

Substances

Carrier Proteins
Inflammasomes
Interleukin-1beta
Intracellular Signaling Peptides and Proteins
NLR Family, Pyrin Domain-Containing 3 Protein
NLRC5 protein, human
NLRP3 protein, human
Viral Proteins