Pathways of IL-1β secretion by macrophages infected with clinical Mycobacterium tuberculosis strains
File(s)
Published version
Author(s)
Krishnan, N
Robertson, BD
Thwaites, G
Type
Journal Article
Abstract
The pro-inflammatory cytokine IL-1β is a key mediator of inflammation and plays an important role in the host resistance to Mycobacterium tuberculosis infections. To date, most studies have examined the mechanisms of IL-1β secretion using laboratory strains of M. tuberculosis and the findings may not be widely applicable to contemporary clinical strains. Here, we investigated the primary pathways of IL-1β secretion in macrophages infected with a panel of 17 clinical M. tuberculosis isolates, representing Euro-American, Indo-Oceanic and East-Asian/Beijing lineages. Our aim was to dissect the pathways involved in M. tuberculosis induced IL-1β secretion and to determine whether they are common to all clinical isolates. We found that the isolates were capable of eliciting variable concentrations of IL-1β from infected murine macrophages, but this phenomenon could not be attributed to differential IL-1β mRNA transcription or pro-IL-1β accumulation. We demonstrate that viable bacteria are required to induce IL-1β secretion from macrophages, but IL-1β secretion was only partially abrogated by caspase-1 inhibition. Almost complete IL-1β secretion inhibition was produced with combined caspase-1 and some serine protease inhibitors. Taken together, these findings demonstrate that clinical strains of M. tuberculosis employ a unique caspase-1 independent pathway to stimulate IL-1β secretion from macrophages.
Date Issued
2013-07-09
Date Acceptance
2013-05-14
Citation
Tuberculosis, 2013, 93 (5), pp.538-547
ISSN
1873-281X
Publisher
Elsevier
Start Page
538
End Page
547
Journal / Book Title
Tuberculosis
Volume
93
Issue
5
Copyright Statement
Open access under CC BY license.
License URL
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Microbiology
Respiratory System
IMMUNOLOGY
MICROBIOLOGY
RESPIRATORY SYSTEM
Mycobacteria
Interleukin-1 beta
Macrophages
Serine proteases
Caspase-1
CASPASE-INDEPENDENT PATHWAY
BACILLUS-CALMETTE-GUERIN
CELL-DEATH
INFLAMMASOME
ACTIVATION
INDUCTION
INTERLEUKIN-1-BETA
APOPTOSIS
RECEPTOR
ATTENUATION
Interleukin-1β
Animals
Apoptosis
Caspase 1
Cells, Cultured
Enzyme Activation
Female
Genotype
Interleukin-1beta
Mice
Mice, Inbred BALB C
Mycobacterium tuberculosis
RNA, Messenger
Serine Proteinase Inhibitors
Signal Transduction
Species Specificity
Tuberculosis
Virulence
11 Medical And Health Sciences
Publication Status
Published