Salmonella Promotes ASC Oligomerization-dependent Caspase-1 Activation
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초록
Innate immune cells sense and respond to the cytoplasmic infection of bacterial pathogens through NLRP3, NLRC4 or AIM2 inflammasome depending on the unique molecular pattern of invading pathogens. The infection of flagellin- or type III secretion system (T3SS)-containing Gram-negative bacteria such as Salmonella enterica serovar Typhimurium (S. typhimurium) or Pseudomonas aeruginosa (P. aeruginosa)triggers NLRC4-dependent caspase-1 activation leading to the secretion of proinflammatory cytokines such as interleukin-1-beta (IL-1β) and IL-18. Previous studies have shown that apoptosis-associated speck-like protein containing a CARD (ASC) is also required for Salmonella-induced caspase-1 activation, but it is still unclear how ASC contributes to the activation of NLRC4 inflammasome in response to S. typhimurium infection. In this study, we demonstrate that S. typhimurium triggers the formation of ASC oligomer in a potassium depletion-independent manner as determined by in vitro crosslinking and in situ fluorescence imaging. Remarkably,inhibition of potassium efflux failed to block Salmonellapromoted caspase-1 activation and macrophage cell death. These results collectively suggest that ASC is substantially oligomerized to facilitate the activation of caspase-1 in response to S. typhimurium infection. Contrary to NLRP3 inflammasome,intracellular potassium depletion is not critical for NLRC4 inflammasome signaling by S. typhimurium.
Abstract
Innate immune cells sense and respond to the cytoplasmic infection of bacterial pathogens through NLRP3, NLRC4 or AIM2 inflammasome depending on the unique molecular pattern of invading pathogens. The infection of flagellin- or type III secretion system (T3SS)-containing Gram-negative bacteria such as Salmonella enterica serovar Typhimurium (S. typhimurium) or Pseudomonas aeruginosa (P. aeruginosa)triggers NLRC4-dependent caspase-1 activation leading to the secretion of proinflammatory cytokines such as interleukin-1-beta (IL-1β) and IL-18. Previous studies have shown that apoptosis-associated speck-like protein containing a CARD (ASC) is also required for Salmonella-induced caspase-1 activation, but it is still unclear how ASC contributes to the activation of NLRC4 inflammasome in response to S. typhimurium infection. In this study, we demonstrate that S. typhimurium triggers the formation of ASC oligomer in a potassium depletion-independent manner as determined by in vitro crosslinking and in situ fluorescence imaging. Remarkably,inhibition of potassium efflux failed to block Salmonellapromoted caspase-1 activation and macrophage cell death. These results collectively suggest that ASC is substantially oligomerized to facilitate the activation of caspase-1 in response to S. typhimurium infection. Contrary to NLRP3 inflammasome,intracellular potassium depletion is not critical for NLRC4 inflammasome signaling by S. typhimurium.
참고문헌 (23)
- Strowig, T., "Inflammasomes in health and disease", Nature, 481, pp.278~286 (2012)
- Sujeong Hong, "Pyrin Domain (PYD)-containing Inflammasome in Innate Immunity", Journal of Bacteriology and Virology, 41(3), pp.133~146 (2011), 대한미생물학회
- 유제욱, "The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation", CELL DEATH AND DIFFERENTIATION, 14(9), pp.1590~1604
- Fernandes-Alnemri, T., "AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA", NATURE, 458(7237), pp.509~5, NATURE PUBLISHING GROUP
- Elinav, E., "Regulation of the antimicrobial response by NLRproteins", Immunity, 34, pp.665~679 (2011)
- Gabriel Nunez, "Sensing and reacting to microbes through the inflammasomes", NATURE IMMUNOLOGY, 13(4), pp.325~332, NATURE PUBLISHING GROUP
- Miao, E. A., "Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf", Nat. Immunol, 7, pp.569~575 (2006)
- Franchi, L, "Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages", Nat. Immunol, 7, pp.576~582 (2006)
- Miao, E. A, "Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome", Proc. Natl. Acad. Sci. U.S.A, 107, pp.3076~3080 (2010)
- Kofoed, E. M, "Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity", Nature, 477, pp.592~595 (2011)
- Zhao, Y., "The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus", Nature, 477, pp.596~600 (2011)
- Fernandes-Alnemri, T., "The AIM2 inflammasome is critical for innate immunity to Francisella tularensis", Nat. Immunol, 11, pp.385~393 (2010)
- Poyet, J. L, "Identification of Ipaf, a human caspase-1-activating protein related to Apaf-1", J. Biol. Chem, 276, pp.28309~28313 (2001)
- Mariathasan, S., "Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf", Nature, 430, pp.213~218 (2004)
- Mariathasan, S., "Cryopyrin activates the inflammasome in response to toxins and ATP", Nature, 440, pp.228~232 (2006)
- Broz. P., "Differential requirement for Caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing", Cell Host Microbe, 8, pp.471~483 (2010)
- Hornung, V., "Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization", Nat. Immunol, 9, pp.847~856 (2008)
- Yu, J. W, "Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants", Mol. Cell, 28, pp.214~227 (2007)
- Pétrilli, V., "Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration", Cell Death Differ, 14, pp.1583~1589 (2007)
- Eisenbarth, S. C., "Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants", Nature, 453, pp.1122~1126 (2008)
- Broz, P., "Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella", J. Exp. Med, 207, pp.1745~1755 (2010)
- Franchi, L., "Differential requirement of P2X7 receptor and intracellularK＋ for caspase-1 activation induced by intracellularand extracellular bacteria", J. Biol. Chem, 282, pp.18810~18818 (2007)
- Arlehamn, C. S., "The role of potassium in inflammasome activation by bacteria", J. Biol. Chem, 285, pp.10508~10518 (2010)