Impaired NLRP3 inflammasome function in elderly mice during influenza infection is rescued by treatment with nigericin.

Abstract	The NLRP3 inflammasome is activated in the lung during influenza viral infection; however, the impact of aging on inflammasome function during influenza infection has not been examined. In this study, we show that elderly mice infected with a mouse-adapted strain of influenza produced lower levels of IL-1β during in vitro and in vivo infection. Dendritic cells from elderly mice exhibited decreased expression of ASC, NLRP3, and capase-1 but increased expression of pro-IL-1β, pro-IL-18, and pro-IL-33 compared with dendritic cells from young infected mice. Treatment with nigericin during influenza infection augmented IL-1β production, increased caspase-1 activity, and decreased morbidity and mortality in elderly mice. Our study demonstrates for the first time, to our knowledge, that during influenza viral infection, elderly mice have impaired NLRP3 inflammasome activity and that treatment with nigericin rescues NLRP3 activation in elderly hosts.
Authors	Heather W Stout-Delgado, Sarah E Vaughan, Anushree C Shirali, Richard J Jaramillo, Kevin S Harrod
Journal	Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 188 Issue 6 Pg. 2815-24 (Mar 15 2012) ISSN: 1550-6606 [Electronic] United States
PMID	22327078 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Antiviral Agents Carrier Proteins Inflammasomes NLR Family, Pyrin Domain-Containing 3 Protein Nlrp3 protein, mouse Caspase 1 Nigericin
Topics	Adoptive Transfer Aging (immunology, metabolism) Animals Antiviral Agents (pharmacology) Blotting, Western Carrier Proteins (immunology, metabolism) Caspase 1 (immunology, metabolism) Disease Models, Animal Enzyme-Linked Immunosorbent Assay Female Inflammasomes (drug effects, immunology, metabolism) Male Mice Mice, Inbred BALB C NLR Family, Pyrin Domain-Containing 3 Protein Nigericin (pharmacology) Orthomyxoviridae Infections (immunology, metabolism) Real-Time Polymerase Chain Reaction

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