CASP4/caspase-11 promotes autophagosome formation in response to bacterial infection

Kathrin Krause, Kyle Caution, Asmaa Badr, Kaitlin Hamilton, Abdulmuti Saleh, Khushbu Patel, Stephanie Seveau, Luanne Hall-Stoodley, Rana Hegazi, Xiaoli Zhang, Mikhail A. Gavrilin, Amal O. Amer

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

CASP4/caspase-11-dependent inflammasome activation is important for the clearance of various Gram-negative bacteria entering the host cytosol. Additionally, CASP4 modulates the actin cytoskeleton to promote the maturation of phagosomes harboring intracellular pathogens such as Legionella pneumophila but not those enclosing nonpathogenic bacteria. Nevertheless, this non-inflammatory role of CASP4 regarding the trafficking of vacuolar bacteria remains poorly understood. Macroautophagy/autophagy, a catabolic process within eukaryotic cells, is also implicated in the elimination of intracellular pathogens such as Burkholderia cenocepacia. Here we show that CASP4-deficient macrophages exhibit a defect in autophagosome formation in response to B. cenocepacia infection. The absence of CASP4 causes an accumulation of the small GTPase RAB7, reduced colocalization of B. cenocepacia with LC3 and acidic compartments accompanied by increased bacterial replication in vitro and in vivo. Together, our data reveal a novel role of CASP4 in regulating autophagy in response to B. cenocepacia infection.

Original languageEnglish (US)
Pages (from-to)1928-1942
Number of pages15
JournalAutophagy
Volume14
Issue number11
DOIs
StatePublished - Nov 2 2018

Fingerprint

Burkholderia cenocepacia
Caspases
Bacterial Infections
Autophagy
Burkholderia Infections
Inflammasomes
Bacteria
Legionella pneumophila
Phagosomes
Monomeric GTP-Binding Proteins
Eukaryotic Cells
Gram-Negative Bacteria
Actin Cytoskeleton
Cytosol
Macrophages
Autophagosomes

Keywords

  • autophagy
  • Burkholderia cenocepacia
  • caspase-1 (CASP1)
  • caspase-11 (CASP4)
  • lysosome
  • macrophages

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Krause, K., Caution, K., Badr, A., Hamilton, K., Saleh, A., Patel, K., ... Amer, A. O. (2018). CASP4/caspase-11 promotes autophagosome formation in response to bacterial infection. Autophagy, 14(11), 1928-1942. https://doi.org/10.1080/15548627.2018.1491494

CASP4/caspase-11 promotes autophagosome formation in response to bacterial infection. / Krause, Kathrin; Caution, Kyle; Badr, Asmaa; Hamilton, Kaitlin; Saleh, Abdulmuti; Patel, Khushbu; Seveau, Stephanie; Hall-Stoodley, Luanne; Hegazi, Rana; Zhang, Xiaoli; Gavrilin, Mikhail A.; Amer, Amal O.

In: Autophagy, Vol. 14, No. 11, 02.11.2018, p. 1928-1942.

Research output: Contribution to journalArticle

Krause, K, Caution, K, Badr, A, Hamilton, K, Saleh, A, Patel, K, Seveau, S, Hall-Stoodley, L, Hegazi, R, Zhang, X, Gavrilin, MA & Amer, AO 2018, 'CASP4/caspase-11 promotes autophagosome formation in response to bacterial infection', Autophagy, vol. 14, no. 11, pp. 1928-1942. https://doi.org/10.1080/15548627.2018.1491494
Krause, Kathrin ; Caution, Kyle ; Badr, Asmaa ; Hamilton, Kaitlin ; Saleh, Abdulmuti ; Patel, Khushbu ; Seveau, Stephanie ; Hall-Stoodley, Luanne ; Hegazi, Rana ; Zhang, Xiaoli ; Gavrilin, Mikhail A. ; Amer, Amal O. / CASP4/caspase-11 promotes autophagosome formation in response to bacterial infection. In: Autophagy. 2018 ; Vol. 14, No. 11. pp. 1928-1942.
@article{d49a28269fc1479bbea41156abc23269,
title = "CASP4/caspase-11 promotes autophagosome formation in response to bacterial infection",
abstract = "CASP4/caspase-11-dependent inflammasome activation is important for the clearance of various Gram-negative bacteria entering the host cytosol. Additionally, CASP4 modulates the actin cytoskeleton to promote the maturation of phagosomes harboring intracellular pathogens such as Legionella pneumophila but not those enclosing nonpathogenic bacteria. Nevertheless, this non-inflammatory role of CASP4 regarding the trafficking of vacuolar bacteria remains poorly understood. Macroautophagy/autophagy, a catabolic process within eukaryotic cells, is also implicated in the elimination of intracellular pathogens such as Burkholderia cenocepacia. Here we show that CASP4-deficient macrophages exhibit a defect in autophagosome formation in response to B. cenocepacia infection. The absence of CASP4 causes an accumulation of the small GTPase RAB7, reduced colocalization of B. cenocepacia with LC3 and acidic compartments accompanied by increased bacterial replication in vitro and in vivo. Together, our data reveal a novel role of CASP4 in regulating autophagy in response to B. cenocepacia infection.",
keywords = "autophagy, Burkholderia cenocepacia, caspase-1 (CASP1), caspase-11 (CASP4), lysosome, macrophages",
author = "Kathrin Krause and Kyle Caution and Asmaa Badr and Kaitlin Hamilton and Abdulmuti Saleh and Khushbu Patel and Stephanie Seveau and Luanne Hall-Stoodley and Rana Hegazi and Xiaoli Zhang and Gavrilin, {Mikhail A.} and Amer, {Amal O.}",
year = "2018",
month = "11",
day = "2",
doi = "10.1080/15548627.2018.1491494",
language = "English (US)",
volume = "14",
pages = "1928--1942",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Landes Bioscience",
number = "11",

}

TY - JOUR

T1 - CASP4/caspase-11 promotes autophagosome formation in response to bacterial infection

AU - Krause, Kathrin

AU - Caution, Kyle

AU - Badr, Asmaa

AU - Hamilton, Kaitlin

AU - Saleh, Abdulmuti

AU - Patel, Khushbu

AU - Seveau, Stephanie

AU - Hall-Stoodley, Luanne

AU - Hegazi, Rana

AU - Zhang, Xiaoli

AU - Gavrilin, Mikhail A.

AU - Amer, Amal O.

PY - 2018/11/2

Y1 - 2018/11/2

N2 - CASP4/caspase-11-dependent inflammasome activation is important for the clearance of various Gram-negative bacteria entering the host cytosol. Additionally, CASP4 modulates the actin cytoskeleton to promote the maturation of phagosomes harboring intracellular pathogens such as Legionella pneumophila but not those enclosing nonpathogenic bacteria. Nevertheless, this non-inflammatory role of CASP4 regarding the trafficking of vacuolar bacteria remains poorly understood. Macroautophagy/autophagy, a catabolic process within eukaryotic cells, is also implicated in the elimination of intracellular pathogens such as Burkholderia cenocepacia. Here we show that CASP4-deficient macrophages exhibit a defect in autophagosome formation in response to B. cenocepacia infection. The absence of CASP4 causes an accumulation of the small GTPase RAB7, reduced colocalization of B. cenocepacia with LC3 and acidic compartments accompanied by increased bacterial replication in vitro and in vivo. Together, our data reveal a novel role of CASP4 in regulating autophagy in response to B. cenocepacia infection.

AB - CASP4/caspase-11-dependent inflammasome activation is important for the clearance of various Gram-negative bacteria entering the host cytosol. Additionally, CASP4 modulates the actin cytoskeleton to promote the maturation of phagosomes harboring intracellular pathogens such as Legionella pneumophila but not those enclosing nonpathogenic bacteria. Nevertheless, this non-inflammatory role of CASP4 regarding the trafficking of vacuolar bacteria remains poorly understood. Macroautophagy/autophagy, a catabolic process within eukaryotic cells, is also implicated in the elimination of intracellular pathogens such as Burkholderia cenocepacia. Here we show that CASP4-deficient macrophages exhibit a defect in autophagosome formation in response to B. cenocepacia infection. The absence of CASP4 causes an accumulation of the small GTPase RAB7, reduced colocalization of B. cenocepacia with LC3 and acidic compartments accompanied by increased bacterial replication in vitro and in vivo. Together, our data reveal a novel role of CASP4 in regulating autophagy in response to B. cenocepacia infection.

KW - autophagy

KW - Burkholderia cenocepacia

KW - caspase-1 (CASP1)

KW - caspase-11 (CASP4)

KW - lysosome

KW - macrophages

UR - http://www.scopus.com/inward/record.url?scp=85053421251&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053421251&partnerID=8YFLogxK

U2 - 10.1080/15548627.2018.1491494

DO - 10.1080/15548627.2018.1491494

M3 - Article

C2 - 30165781

AN - SCOPUS:85053421251

VL - 14

SP - 1928

EP - 1942

JO - Autophagy

JF - Autophagy

SN - 1554-8627

IS - 11

ER -