In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 7 ( 2021-7-29), p. e1009712-
Abstract:
Mycobacterium tuberculosis (Mtb) has evolved to evade host innate immunity by interfering with macrophage functions. Interleukin-1β (IL-1β) is secreted by macrophages after the activation of the inflammasome complex and is crucial for host defense against Mtb infections. We have previously shown that Mtb is able to inhibit activation of the AIM2 inflammasome and subsequent pyroptosis. Here we show that Mtb is also able to inhibit host cell NLRP3 inflammasome activation and pyroptosis. We identified the serine/threonine kinase PknF as one protein of Mtb involved in the NLRP3 inflammasome inhibition, since the pknF deletion mutant of Mtb induces increased production of IL-1β in bone marrow-derived macrophages (BMDMs). The increased production of IL-1β was dependent on NLRP3, the adaptor protein ASC and the protease caspase-1, as revealed by studies performed in gene-deficient BMDMs. Additionally, infection of BMDMs with the pknF deletion mutant resulted in increased pyroptosis, while the IL-6 production remained unchanged compared to Mtb-infected cells, suggesting that the mutant did not affect the priming step of inflammasome activation. In contrast, the activation step was affected since potassium efflux, chloride efflux and the generation of reactive oxygen species played a significant role in inflammasome activation and subsequent pyroptosis mediated by the Mtb pknF mutant strain. In conclusion, we reveal here that the serine/threonine kinase PknF of Mtb plays an important role in innate immune evasion through inhibition of the NLRP3 inflammasome.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009712
DOI:
10.1371/journal.ppat.1009712.g001
DOI:
10.1371/journal.ppat.1009712.g002
DOI:
10.1371/journal.ppat.1009712.g003
DOI:
10.1371/journal.ppat.1009712.g004
DOI:
10.1371/journal.ppat.1009712.g005
DOI:
10.1371/journal.ppat.1009712.g006
DOI:
10.1371/journal.ppat.1009712.g007
DOI:
10.1371/journal.ppat.1009712.s001
DOI:
10.1371/journal.ppat.1009712.s002
DOI:
10.1371/journal.ppat.1009712.s003
DOI:
10.1371/journal.ppat.1009712.s004
DOI:
10.1371/journal.ppat.1009712.s005
DOI:
10.1371/journal.ppat.1009712.s006
DOI:
10.1371/journal.ppat.1009712.s007
DOI:
10.1371/journal.ppat.1009712.s008
DOI:
10.1371/journal.ppat.1009712.s009
DOI:
10.1371/journal.ppat.1009712.s010
DOI:
10.1371/journal.ppat.1009712.s011
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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