title: Participation of Necroptosis in the Host Response to Acute Bacterial Pneumonia.
abstract: Common pulmonary pathogens, such as Streptococcus pneumoniae and Staphylococcus aureus, as well as the host-adapted pathogens responsible for health care-associated pneumonias, such as the carbapenem-resistant Klebsiella pneumoniae and Serratia marcecsens, are able to activate cell death through the RIPK1/RIPK3/MLKL cascade that causes necroptosis. Necroptosis can influence the pathogenesis of pneumonia through several mechanisms. Activation of this pathway can result in the loss of specific types of immune cells, especially macrophages, and, in so doing, contribute to host pathology through the loss of their critical immunoregulatory functions. However, in other settings of infection, necroptosis promotes pathogen removal and the eradication of infected cells to control excessive proinflammatory signaling. Bacterial production of pore-forming toxins provides a common mechanism to activate necroptosis by diverse bacterial species, with variable consequences depending upon the specific pathogen. Included in this brief review are data demonstrating the ability of the carbapenem-resistant ST258 K. pneumoniae to activate necroptosis in the setting of pneumonia, which is counterbalanced by their suppression of CYLD expression. Exactly how necroptosis and other mechanisms of cell death are coregulated in the response to specific pulmonary pathogens remains a topic of active investigation, and it may provide potential therapeutic targets in the future.
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Ahn
authors.forename: Alice
authors.initials: A
authors.lastname: Prince
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D000074749:Deubiquitinating Enzyme CYLD / Q000378:metabolism; D006801:Humans; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008168:Lung / Q000382:microbiology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D009336:Necrosis; D018410:Pneumonia, Bacterial / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD
keywords: Bacterial pneumonia; Cellular death; Necroptosis