Viral Infection Augments Nod1/2 Signaling to Potentiate Lethality Associated with Secondary Bacterial Infections

Publication year: 2011
Source: Cell Host & Microbe, Volume 9, Issue 6, 16 June 2011, Pages 496-507

Yun-Gi, Kim , Jong-Hwan, Park , Thornik, Reimer , Darren P., Baker , Taro, Kawai , …

Secondary bacterial infection is a common sequela to viral infection and is associated with increased lethality and morbidity. However, the underlying mechanisms remain poorly understood. We show that the TLR3/MDA5 agonist poly I:C or viral infection dramatically augments signaling via the NLRs Nod1 and Nod2 and enhances the production of proinflammatory cytokines. Enhanced Nod1 and Nod2 signaling by poly I:C required the TLR3/MDA5 adaptors TRIF and IPS-1 and was mediated by type I IFNs. Mechanistically, poly I:C or IFN-β induced the expression of Nod1, Nod2, and the Nod-signaling adaptor Rip2. Systemic administration of poly I:C or IFN-β or infection with murine…

 Highlights: ► Viral infection augments Nod1 and Nod2 activation via the production of type I IFNs ► Type I IFN signaling induces expression of Nod1, Nod2, and Rip2 ► Nod1/Nod2 potentiate susceptibility to bacterial infection in virally infected mice ► IFN-β enhances bacteria-induced lethality via Nod1 and Nod2