Deletion of ripA alleviates suppression of the inflammasome and MAPK by Francisella tularensis

Max Tze Han Huang, Brittany L. Mortensen, Debra J. Taxman, Robin R. Craven, Sharon Taft-Benz, Todd M. Kijek, James R. Fuller, Beckley K. Davis, Irving Coy Allen, Willie June Brickey, Denis Gris, Haitao Wen, Thomas H. Kawula, Jenny Pan Yun Ting

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Francisella tularensis is a facultative intracellular pathogen and potential biothreat agent. Evasion of the immune response contributes to the extraordinary virulence of this organism although the mechanism is unclear. Whereas wild-type strains induced low levels of cytokines, an F. tularensis ripA deletion mutant (LVSDripA) provoked significant release of IL-1β, IL-18, and TNF-a by resting macrophages. IL-1β and IL-18 secretion was dependent on inflammasome components pyrin-caspase recruitment domain/apoptotic speck-containing protein with a caspase recruitment domain and caspase-1, and the TLR/IL-1R signaling molecule MyD88 was required for inflammatory cytokine synthesis. Complementation of LVSΔripA with a plasmid encoding ripA restored immune evasion. Similar findings were observed in a human monocytic line. The presence of ripA nearly eliminated activation of MAPKs including ERK1/2, JNK, and p38, and pharmacologic inhibitors of these three MAPKs reduced cytokine induction by LVSΔripA. Animals infected with LVSΔripA mounted a stronger IL-1β and TNF-α response than that of mice infected with wild-type live vaccine strain.

Original languageEnglish (US)
Pages (from-to)5476-5485
Number of pages10
JournalJournal of Immunology
Volume185
Issue number9
DOIs
StatePublished - Nov 1 2010

Fingerprint

Francisella tularensis
Inflammasomes
Interleukin-1
Immune Evasion
Interleukin-18
Cytokines
Caspase 1
Virulence
Plasmids
Vaccines
Macrophages
Proteins
Caspase Activation and Recruitment Domain

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Huang, M. T. H., Mortensen, B. L., Taxman, D. J., Craven, R. R., Taft-Benz, S., Kijek, T. M., ... Ting, J. P. Y. (2010). Deletion of ripA alleviates suppression of the inflammasome and MAPK by Francisella tularensis. Journal of Immunology, 185(9), 5476-5485. https://doi.org/10.4049/jimmunol.1002154

Deletion of ripA alleviates suppression of the inflammasome and MAPK by Francisella tularensis. / Huang, Max Tze Han; Mortensen, Brittany L.; Taxman, Debra J.; Craven, Robin R.; Taft-Benz, Sharon; Kijek, Todd M.; Fuller, James R.; Davis, Beckley K.; Allen, Irving Coy; Brickey, Willie June; Gris, Denis; Wen, Haitao; Kawula, Thomas H.; Ting, Jenny Pan Yun.

In: Journal of Immunology, Vol. 185, No. 9, 01.11.2010, p. 5476-5485.

Research output: Contribution to journalArticle

Huang, MTH, Mortensen, BL, Taxman, DJ, Craven, RR, Taft-Benz, S, Kijek, TM, Fuller, JR, Davis, BK, Allen, IC, Brickey, WJ, Gris, D, Wen, H, Kawula, TH & Ting, JPY 2010, 'Deletion of ripA alleviates suppression of the inflammasome and MAPK by Francisella tularensis', Journal of Immunology, vol. 185, no. 9, pp. 5476-5485. https://doi.org/10.4049/jimmunol.1002154
Huang MTH, Mortensen BL, Taxman DJ, Craven RR, Taft-Benz S, Kijek TM et al. Deletion of ripA alleviates suppression of the inflammasome and MAPK by Francisella tularensis. Journal of Immunology. 2010 Nov 1;185(9):5476-5485. https://doi.org/10.4049/jimmunol.1002154
Huang, Max Tze Han ; Mortensen, Brittany L. ; Taxman, Debra J. ; Craven, Robin R. ; Taft-Benz, Sharon ; Kijek, Todd M. ; Fuller, James R. ; Davis, Beckley K. ; Allen, Irving Coy ; Brickey, Willie June ; Gris, Denis ; Wen, Haitao ; Kawula, Thomas H. ; Ting, Jenny Pan Yun. / Deletion of ripA alleviates suppression of the inflammasome and MAPK by Francisella tularensis. In: Journal of Immunology. 2010 ; Vol. 185, No. 9. pp. 5476-5485.
@article{7e534a0e805f45598295d5272bf298c1,
title = "Deletion of ripA alleviates suppression of the inflammasome and MAPK by Francisella tularensis",
abstract = "Francisella tularensis is a facultative intracellular pathogen and potential biothreat agent. Evasion of the immune response contributes to the extraordinary virulence of this organism although the mechanism is unclear. Whereas wild-type strains induced low levels of cytokines, an F. tularensis ripA deletion mutant (LVSDripA) provoked significant release of IL-1β, IL-18, and TNF-a by resting macrophages. IL-1β and IL-18 secretion was dependent on inflammasome components pyrin-caspase recruitment domain/apoptotic speck-containing protein with a caspase recruitment domain and caspase-1, and the TLR/IL-1R signaling molecule MyD88 was required for inflammatory cytokine synthesis. Complementation of LVSΔripA with a plasmid encoding ripA restored immune evasion. Similar findings were observed in a human monocytic line. The presence of ripA nearly eliminated activation of MAPKs including ERK1/2, JNK, and p38, and pharmacologic inhibitors of these three MAPKs reduced cytokine induction by LVSΔripA. Animals infected with LVSΔripA mounted a stronger IL-1β and TNF-α response than that of mice infected with wild-type live vaccine strain.",
author = "Huang, {Max Tze Han} and Mortensen, {Brittany L.} and Taxman, {Debra J.} and Craven, {Robin R.} and Sharon Taft-Benz and Kijek, {Todd M.} and Fuller, {James R.} and Davis, {Beckley K.} and Allen, {Irving Coy} and Brickey, {Willie June} and Denis Gris and Haitao Wen and Kawula, {Thomas H.} and Ting, {Jenny Pan Yun}",
year = "2010",
month = "11",
day = "1",
doi = "10.4049/jimmunol.1002154",
language = "English (US)",
volume = "185",
pages = "5476--5485",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

TY - JOUR

T1 - Deletion of ripA alleviates suppression of the inflammasome and MAPK by Francisella tularensis

AU - Huang, Max Tze Han

AU - Mortensen, Brittany L.

AU - Taxman, Debra J.

AU - Craven, Robin R.

AU - Taft-Benz, Sharon

AU - Kijek, Todd M.

AU - Fuller, James R.

AU - Davis, Beckley K.

AU - Allen, Irving Coy

AU - Brickey, Willie June

AU - Gris, Denis

AU - Wen, Haitao

AU - Kawula, Thomas H.

AU - Ting, Jenny Pan Yun

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Francisella tularensis is a facultative intracellular pathogen and potential biothreat agent. Evasion of the immune response contributes to the extraordinary virulence of this organism although the mechanism is unclear. Whereas wild-type strains induced low levels of cytokines, an F. tularensis ripA deletion mutant (LVSDripA) provoked significant release of IL-1β, IL-18, and TNF-a by resting macrophages. IL-1β and IL-18 secretion was dependent on inflammasome components pyrin-caspase recruitment domain/apoptotic speck-containing protein with a caspase recruitment domain and caspase-1, and the TLR/IL-1R signaling molecule MyD88 was required for inflammatory cytokine synthesis. Complementation of LVSΔripA with a plasmid encoding ripA restored immune evasion. Similar findings were observed in a human monocytic line. The presence of ripA nearly eliminated activation of MAPKs including ERK1/2, JNK, and p38, and pharmacologic inhibitors of these three MAPKs reduced cytokine induction by LVSΔripA. Animals infected with LVSΔripA mounted a stronger IL-1β and TNF-α response than that of mice infected with wild-type live vaccine strain.

AB - Francisella tularensis is a facultative intracellular pathogen and potential biothreat agent. Evasion of the immune response contributes to the extraordinary virulence of this organism although the mechanism is unclear. Whereas wild-type strains induced low levels of cytokines, an F. tularensis ripA deletion mutant (LVSDripA) provoked significant release of IL-1β, IL-18, and TNF-a by resting macrophages. IL-1β and IL-18 secretion was dependent on inflammasome components pyrin-caspase recruitment domain/apoptotic speck-containing protein with a caspase recruitment domain and caspase-1, and the TLR/IL-1R signaling molecule MyD88 was required for inflammatory cytokine synthesis. Complementation of LVSΔripA with a plasmid encoding ripA restored immune evasion. Similar findings were observed in a human monocytic line. The presence of ripA nearly eliminated activation of MAPKs including ERK1/2, JNK, and p38, and pharmacologic inhibitors of these three MAPKs reduced cytokine induction by LVSΔripA. Animals infected with LVSΔripA mounted a stronger IL-1β and TNF-α response than that of mice infected with wild-type live vaccine strain.

UR - http://www.scopus.com/inward/record.url?scp=78149489515&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78149489515&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1002154

DO - 10.4049/jimmunol.1002154

M3 - Article

C2 - 20921527

AN - SCOPUS:78149489515

VL - 185

SP - 5476

EP - 5485

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -