IRGB10 Liberates Bacterial Ligands for Sensing by the AIM2 and Caspase-11-NLRP3 Inflammasomes

Si Ming Man; Rajendra Karki; Miwa Sasai; David E. Place; Sannula Kesavardhana; Jamshid Temirov; Sharon Frase; Qifan Zhu; R. K.Subbarao Malireddi; Teneema Kuriakose; Jennifer L. Peters; Geoffrey Neale; Scott A. Brown; Masahiro Yamamoto; Thirumala Devi Kanneganti

doi:10.1016/j.cell.2016.09.012

IRGB10 Liberates Bacterial Ligands for Sensing by the AIM2 and Caspase-11-NLRP3 Inflammasomes

Si Ming Man, Rajendra Karki, Miwa Sasai, David E. Place, Sannula Kesavardhana, Jamshid Temirov, Sharon Frase, Qifan Zhu, R. K.Subbarao Malireddi, Teneema Kuriakose, Jennifer L. Peters, Geoffrey Neale, Scott A. Brown, Masahiro Yamamoto, Thirumala Devi Kanneganti^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

242 Citations (Scopus)

Abstract

The inflammasome is an intracellular signaling complex, which on recognition of pathogens and physiological aberration, drives activation of caspase-1, pyroptosis, and the release of the pro-inflammatory cytokines IL-1β and IL-18. Bacterial ligands must secure entry into the cytoplasm to activate inflammasomes; however, the mechanisms by which concealed ligands are liberated in the cytoplasm have remained unclear. Here, we showed that the interferon-inducible protein IRGB10 is essential for activation of the DNA-sensing AIM2 inflammasome by Francisella novicida and contributed to the activation of the LPS-sensing caspase-11 and NLRP3 inflammasome by Gram-negative bacteria. IRGB10 directly targeted cytoplasmic bacteria through a mechanism requiring guanylate-binding proteins. Localization of IRGB10 to the bacterial cell membrane compromised bacterial structural integrity and mediated cytosolic release of ligands for recognition by inflammasome sensors. Overall, our results reveal IRGB10 as part of a conserved signaling hub at the interface between cell-autonomous immunity and innate immune sensing pathways.

Original language	English
Pages (from-to)	382-396.e17
Journal	Cell
Volume	167
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2016.09.012
Publication status	Published - 6 Oct 2016
Externally published	Yes

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Man, S. M., Karki, R., Sasai, M., Place, D. E., Kesavardhana, S., Temirov, J., Frase, S., Zhu, Q., Malireddi, R. K. S., Kuriakose, T., Peters, J. L., Neale, G., Brown, S. A., Yamamoto, M., & Kanneganti, T. D. (2016). IRGB10 Liberates Bacterial Ligands for Sensing by the AIM2 and Caspase-11-NLRP3 Inflammasomes. Cell, 167(2), 382-396.e17. https://doi.org/10.1016/j.cell.2016.09.012

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title = "IRGB10 Liberates Bacterial Ligands for Sensing by the AIM2 and Caspase-11-NLRP3 Inflammasomes",

abstract = "The inflammasome is an intracellular signaling complex, which on recognition of pathogens and physiological aberration, drives activation of caspase-1, pyroptosis, and the release of the pro-inflammatory cytokines IL-1β and IL-18. Bacterial ligands must secure entry into the cytoplasm to activate inflammasomes; however, the mechanisms by which concealed ligands are liberated in the cytoplasm have remained unclear. Here, we showed that the interferon-inducible protein IRGB10 is essential for activation of the DNA-sensing AIM2 inflammasome by Francisella novicida and contributed to the activation of the LPS-sensing caspase-11 and NLRP3 inflammasome by Gram-negative bacteria. IRGB10 directly targeted cytoplasmic bacteria through a mechanism requiring guanylate-binding proteins. Localization of IRGB10 to the bacterial cell membrane compromised bacterial structural integrity and mediated cytosolic release of ligands for recognition by inflammasome sensors. Overall, our results reveal IRGB10 as part of a conserved signaling hub at the interface between cell-autonomous immunity and innate immune sensing pathways.",

keywords = "GBP2, GBP5, GBPs, LPS, caspase-1, cell-autonomous immunity, immunity-related GTPases, innate immunity, interferons, non-canonical inflammasome",

author = "Man, {Si Ming} and Rajendra Karki and Miwa Sasai and Place, {David E.} and Sannula Kesavardhana and Jamshid Temirov and Sharon Frase and Qifan Zhu and Malireddi, {R. K.Subbarao} and Teneema Kuriakose and Peters, {Jennifer L.} and Geoffrey Neale and Brown, {Scott A.} and Masahiro Yamamoto and Kanneganti, {Thirumala Devi}",

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doi = "10.1016/j.cell.2016.09.012",

language = "English",

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AU - Man, Si Ming

AU - Karki, Rajendra

AU - Sasai, Miwa

AU - Place, David E.

AU - Kesavardhana, Sannula

AU - Temirov, Jamshid

AU - Frase, Sharon

AU - Zhu, Qifan

AU - Malireddi, R. K.Subbarao

AU - Kuriakose, Teneema

AU - Peters, Jennifer L.

AU - Neale, Geoffrey

AU - Brown, Scott A.

AU - Yamamoto, Masahiro

AU - Kanneganti, Thirumala Devi

PY - 2016/10/6

Y1 - 2016/10/6

N2 - The inflammasome is an intracellular signaling complex, which on recognition of pathogens and physiological aberration, drives activation of caspase-1, pyroptosis, and the release of the pro-inflammatory cytokines IL-1β and IL-18. Bacterial ligands must secure entry into the cytoplasm to activate inflammasomes; however, the mechanisms by which concealed ligands are liberated in the cytoplasm have remained unclear. Here, we showed that the interferon-inducible protein IRGB10 is essential for activation of the DNA-sensing AIM2 inflammasome by Francisella novicida and contributed to the activation of the LPS-sensing caspase-11 and NLRP3 inflammasome by Gram-negative bacteria. IRGB10 directly targeted cytoplasmic bacteria through a mechanism requiring guanylate-binding proteins. Localization of IRGB10 to the bacterial cell membrane compromised bacterial structural integrity and mediated cytosolic release of ligands for recognition by inflammasome sensors. Overall, our results reveal IRGB10 as part of a conserved signaling hub at the interface between cell-autonomous immunity and innate immune sensing pathways.

AB - The inflammasome is an intracellular signaling complex, which on recognition of pathogens and physiological aberration, drives activation of caspase-1, pyroptosis, and the release of the pro-inflammatory cytokines IL-1β and IL-18. Bacterial ligands must secure entry into the cytoplasm to activate inflammasomes; however, the mechanisms by which concealed ligands are liberated in the cytoplasm have remained unclear. Here, we showed that the interferon-inducible protein IRGB10 is essential for activation of the DNA-sensing AIM2 inflammasome by Francisella novicida and contributed to the activation of the LPS-sensing caspase-11 and NLRP3 inflammasome by Gram-negative bacteria. IRGB10 directly targeted cytoplasmic bacteria through a mechanism requiring guanylate-binding proteins. Localization of IRGB10 to the bacterial cell membrane compromised bacterial structural integrity and mediated cytosolic release of ligands for recognition by inflammasome sensors. Overall, our results reveal IRGB10 as part of a conserved signaling hub at the interface between cell-autonomous immunity and innate immune sensing pathways.

KW - GBP2

KW - GBP5

KW - GBPs

KW - LPS

KW - caspase-1

KW - cell-autonomous immunity

KW - immunity-related GTPases

KW - innate immunity

KW - interferons

KW - non-canonical inflammasome

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DO - 10.1016/j.cell.2016.09.012

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SP - 382-396.e17

JO - Cell

JF - Cell

IS - 2

ER -

IRGB10 Liberates Bacterial Ligands for Sensing by the AIM2 and Caspase-11-NLRP3 Inflammasomes

Abstract

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