Scientific Publications by FDA Staff

Infect Immun 2009 Oct;77(10):4529-37

Nod1/Nod2-mediated recognition plays a critical role in induction of adaptive immunity to anthrax after aerosol exposure.

Loving CL, Osorio M, Kim YG, Nuñez G, Hughes MA, Merkel TJ

TLR and Nod-like receptors (NLR) play an important role in sensing invading microorganisms for pathogen clearance and eliciting adaptive immunity for protection to rechallenge. Nod1 and Nod2, members of the NLR family, are capable of detecting bacterial peptidoglycan motifs in the host cytosol for triggering proinflammatory cytokine production. In the current study, we sought to determine if Nod1/Nod2 are involved in sensing B. anthracis infection and eliciting protective immune responses. Using mice deficient for both Nod1 and Nod2 proteins, we show that Nod1/Nod2 is involved in detecting B. anthracis for production of TNF-alpha, IL-1alpha, IL-1beta, CCL5, IL-6, and KC. Proinflammatory responses were higher when cells were exposed to viable spores compared to irradiated spores, indicating that recognition of vegetative bacilli through Nod1/Nod2 is significant. We also identify a critical role for Nod1/Nod2 in priming responses after B. anthracis aerosol exposure, as mice deficient for Nod1/Nod2 were impaired in their ability to mount an anamnestic antibody response and were more susceptible to secondary lethal challenge compared to wild-type mice.