Targeting NLRP3 and Staphylococcal pore‐forming toxin receptors in human‐induced pluripotent stem cell‐derived macrophages

• Published in: Journal of leukocyte biology Vol. 108; no. 3; pp. 967 - 981
• Main Authors: Chow, Seong H., Deo, Pankaj, Yeung, Amy T. Y., Kostoulias, Xenia P., Jeon, Yusun, Gao, Mei‐Ling, Seidi, Azadeh, Olivier, Françios Alwyn Benson, Sridhar, Sushmita, Nethercott, Cara, Cameron, David, Robertson, Avril A. B., Robert, Remy, Mackay, Charles R., Traven, Ana, Jin, Zi‐Bing, Hale, Christine, Dougan, Gordon, Peleg, Anton Y., Naderer, Thomas
• Format: Journal Article
• Language: English
• Published: United States 01.09.2020
• Subjects: Animals; Bacterial Proteins - antagonists & inhibitors; Bacterial Toxins - antagonists & inhibitors; CD11b Antigen - immunology; Cell Differentiation; Cells, Cultured; CRISPR-Cas Systems; Exotoxins - antagonists & inhibitors; Exotoxins - deficiency; Gene Knock-In Techniques; Humans; Induced Pluripotent Stem Cells - cytology; inflammation; Interleukin-1beta - metabolism; Leukocidins - antagonists & inhibitors; Leukocyte Common Antigens - physiology; Lung - immunology; Lung - microbiology; macrophage; Macrophages - cytology; Macrophages - drug effects; Macrophages - immunology; Mice; Mice, Inbred C57BL; Monocytes - cytology; NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors; NLRP3; Peptide Fragments - immunology; pneumonia; Pneumonia, Staphylococcal - immunology; Protein Subunits; Receptor, Anaphylatoxin C5a - deficiency; Receptor, Anaphylatoxin C5a - drug effects; Receptor, Anaphylatoxin C5a - genetics; Receptor, Anaphylatoxin C5a - physiology; Recombinant Proteins - metabolism; staphylococcus; Staphylococcus aureus - physiology; toxin; NLRP3; macrophage; pneumonia; toxin; inflammation; staphylococcus

Staphylococcus aureus causes necrotizing pneumonia by secreting toxins such as leukocidins that target front‐line immune cells. The mechanism by which leukocidins kill innate immune cells and trigger inflammation during S. aureus lung infection, however, remains unresolved. Here, we explored human‐i...