Autophagy Defends Cells Against Invading Group A
            <i>Streptococcus</i>

Nakagawa, Ichirô; Amano, Atsuo; Mizushima, Noboru; Yamamoto, Akira; Yamaguchi, Hideyo; Kamimoto, Takeyuki; Nara, Atsuki; Funao, Junko; Nakata, Masao; Tsuda, Kayoko; Hamada, Shigeyuki; Yoshimori, Tamotsu

doi:10.1126/science.1103966

Cited by 1,037 publications

(961 citation statements)

References 18 publications

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“…[44][45][46] Autophagy has an important role in physiological and pathological processes, such as degradation of cytoplasmic components, cellular response to nutrient starvation and apoptosis. 47,48 Moreover, autophagy is also relevant in innate 49,50 and adaptive immunity. 51,52 Atg16l in conjunction with an Atg12-Atg5 conjugate, has a crucial role in the elongation of isolation membranes and the initial step of autophagosome formation, 53 and it is essential in the targeting and destruction of pathogens 49 as well as in foreign (microbial) antigen processing and presentation 52 protecting against viruses, bacteria and other pathogens.…”

Section: Discussionmentioning

confidence: 99%

“…47,48 Moreover, autophagy is also relevant in innate 49,50 and adaptive immunity. 51,52 Atg16l in conjunction with an Atg12-Atg5 conjugate, has a crucial role in the elongation of isolation membranes and the initial step of autophagosome formation, 53 and it is essential in the targeting and destruction of pathogens 49 as well as in foreign (microbial) antigen processing and presentation 52 protecting against viruses, bacteria and other pathogens. The functional role of the ATG16L1 T300A amino-acid substitution (polar proline to nonpolar alanine) is not yet clear, but it lies at the highly evolutionary conserved position 300 in the N terminus of the WD-repeat domain in ATG16L1 and, therefore, may affect protein interactions with other components of the autophagosome.…”

Section: Discussionmentioning

confidence: 99%

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Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach

et al. 2009

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The aim of this study was to determine the role of the ATG16L1 (rs2241880) and IRGM (rs13361189 and rs4958847) genes polymorphism in Crohn's disease (CD) and ulcerative colitis (UC). Our study included 557 CD and 425 UC patients and 672 ethnically matched Spanish controls and a meta-analysis with the data published to date. The polymorphisms were genotyped using predesigned TaqMan single nucleotide polymorphism genotyping assays. There was a statistically significant difference in the distribution of the ATG16L1 rs2241880 G allele between CD patients and controls in the Spanish population: P ¼ 6.5 Â 10 À9 , odds ratio (OR) ¼ 1.62. Although no differences were observed between UC patients and controls in the Spanish cohort, a meta-analysis demonstrated that the ATG16L1 G allele increase significantly risk for UC (P ¼ 0.0003, pooled OR ¼ 1.08). In addition, our meta-analysis data showed that IRGM rs13361189 and rs4958847 polymorphisms were associated with CD (rs13361189 C allele P ¼ 1.07 Â 10 À19 , pooled OR ¼ 1.34; rs4958847 A allele P ¼ 2.78 Â 10 À17 , pooled OR ¼ 1.31) and UC (rs13361189 P ¼ 0.0069, pooled OR ¼ 1.16; rs4958847 P ¼ 0.014, pooled OR ¼ 1.13). In conclusion, our results confirm the ATG16L1 rs2241880 and IRGM rs13361189 and rs4958847 polymorphisms as important markers for CD susceptibility and indicate that these variants are also associated with UC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach

et al. 2009

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“…Nakagawa and Yoshimori's group showed that group A Streptococci (GAS), upon escaping from endosomes into the cytosol by a streptolysin O-mediated process, are immediately and specifically sequestered by autophagosome-like structures. 28 These GAS-containing structures are eventually fused with lysosomes for degradation. The formation of these structures is Atg5-dependent, and in Atg5 À/À embryonic fibroblasts and embryonic fibroblasts, degradation of GAS is significantly reduced, suggesting that this autophagy-like process is indeed bactericidal.…”

Section: Degradation Of Invading Bacteriamentioning

confidence: 99%

The pleiotropic role of autophagy: from protein metabolism to bactericide

2005

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Autophagy is in principle a nonselective, bulk degradation system within cells, with a contribution to intracellular protein degradation estimated to be as large as that of the ubiquitin--proteasome system. The primary roles of autophagy are baseline turnover of intracellular proteins and organelles, production of amino acids in nutrient emergency, and regression of retired tissues. These functions guarantee rejuvenation and adaptation to adverse conditions, and even underlie dynamic processes such as development/metamorphosis. In addition, several other roles for autophagy have recently been discovered, such as presentation of endogenous antigens and degradation of invasive bacteria. This review will discuss the biological significance of autophagy from yeast to higher eukaryotes.

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“…The breakdown of damaged organelles and proteins via autophagy leads to the recycling of nutrients and sustains cellular energy levels. In addition, autophagy targets various intracellular pathogens such as Mycobacterium tuberculosis [1], Salmonella enterica serovar Typhimurium [2], Legionella pneumophila [3], Streptococcus pyogenes [4], and Burkholderia cenocepacia [5]. This bacteria-specific autophagic process, designated xenophagy, promotes bacterial clearance and prevents cellular escape.…”

Section: Introductionmentioning

confidence: 99%

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

Krause¹,

Caution²,

Badr³

et al. 2018

Autophagy

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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.

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Autophagy Defends Cells Against Invading Group A Streptococcus

Cited by 1,037 publications

References 18 publications

Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach

Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach

The pleiotropic role of autophagy: from protein metabolism to bactericide

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

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