Research Interest: Innate Immunity Defenses Against Intracellular Pathogens
Ph.D.: Indiana State University
Postdoctoral: University of North Carolina at Chapel Hill
We study how the innate immunity detect intracellular pathogens and subsequently orchestrate their elimination. We specifically focus on cytosolic pathogen pattern recognition detectors, inflammasomes, which activate caspase-1. Caspase 1 subsequently activates the processing of the pro-inflammatory cytokines pro-IL-1β and pro-IL-18 and/or promotes a form of programmed cell death termed pyroptosis. Pyroptosis restricts intracellular bacterial growth by lysing infected cells, thereby eliminating the intracellular replication niche, and exposing the bacteria to attack by neutrophils. For instance, we showed that the inflammatory caspase-11 discriminates between cytosolic and vacuolar bacteria, and this detection is necessary for protection against cytosolic pathogens such as Burkhloderiaspecies, and the ΔsifA mutant of Salmonella typhimurium that aberrantly exits the vacuole. We went on to show that caspase-11 is activated in response to cytosolic LPS.
Current studies examine the activation of caspase-1 and caspase-11 inflammasomes, and investigates their role in infection and inflammatory disorders.
Kovacs SB, Oh C, Aachoui Y, Miao EA. Evaluating cytokine production by flow cytometry using brefeldin A in mice. STAR Protoc. 2020 Dec 30;2(1):100244.
Oh C, Verma A, Aachoui Y. Caspase-11 Non-canonical Inflammasomes in the Lung. Front Immunol. 2020 Aug 21;11:1895.
Kovacs SB, Oh C, Maltez VI, McGlaughon BD, Verma A, Miao EA, Aachoui Y. Neutrophil Caspase-11 Is Essential to Defend against a Cytosol-Invasive Bacterium. Cell Rep. 2020 Jul 28;32(4):107967.
Aachoui, Y., and Miao, E.A. (2016). Down with doublespeak: NAIP/NLRC4 inflammasomes get specific. The Journal of Experimental Medicine 213, 646
Aachoui, Y., Kajiwara, Y., Leaf, Irina A., Mao, D., Ting, Jenny P.Y., Coers, J., Aderem, A., Buxbaum, Joseph D., and Miao, E.A. (2015). Canonical Inflammasomes Drive IFN-β; to Prime Caspase-11 in Defense against a Cytosol-Invasive Bacterium. Cell Host & Microbe 18, 320-332.
Maltez, Vivien I., Tubbs, Alan L., Cook, Kevin D., Aachoui, Y., Falcone, E.L., Holland, Steven M., Whitmire, Jason K., and Miao, E. A. (2015). Inflammasomes Coordinate Pyroptosis and Natural Killer Cell Cytotoxicity to Clear Infection by a Ubiquitous Environmental Bacterium. Immunity 43, 987-997
Aachoui Y, Leaf IA, Hagar JA, Fontana MF, Campos CG, Zak DE, Tan MH, Cotter PA, Vance RE, Aderem A, Miao E.A. (2013). Caspase11 protects against bacteria that escape the vacuole. Science. 2013 Feb 22;339 (6122):9758.
Hagar JA, Powell DA, Aachoui Y, Ernst RK, Miao E.A.(2013). Cytoplasmic LPS activates caspase11: implications in TLR4independent endotoxic shock. Science. 2013 Sep 13;341(6151):12503.
Aachoui Y, Sagulenko V, Miao EA, Stacey KJ. (2013). Inflammasome mediated pyroptotic and apoptotic cell death, and defense against infection. Curr Opin Microbiol. 2013 Jun;16(3):31926.