title: Nod1/Nod2-mediated recognition plays a critical role in induction of adaptive immunity to anthrax after aerosol exposure.
abstract: Toll-like receptors and Nod-like receptors (NLR) play an important role in sensing invading microorganisms for pathogen clearance and eliciting adaptive immunity for protection against 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 Bacillus anthracis infection and eliciting protective immune responses. Using mice deficient in both Nod1 and Nod2 proteins, we showed that Nod1/Nod2 are involved in detecting B. anthracis for production of tumor necrosis factor alpha, interleukin-1 alpha (IL-1 alpha), IL-1 beta, CCL5, IL-6, and KC. Proinflammatory responses were higher when cells were exposed to viable spores than when they were exposed 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 in Nod1/Nod2 were impaired in their ability to mount an anamnestic antibody response and were more susceptible to secondary lethal challenge than wild-type mice.
authors.affiliation: Laboratory of Respiratory and Special Pathogens, Division of Bacterial, Parasitic and Allergenic Products, CBER, FDA, Bethesda, Maryland, USA.
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Loving
authors.forename: Manuel
authors.initials: M
authors.lastname: Osorio
authors.forename: Yun-Gi
authors.initials: YG
authors.lastname: Kim
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nuñez
authors.forename: Molly A
authors.initials: MA
authors.lastname: Hughes
authors.forename: Tod J
authors.initials: TJ
authors.lastname: Merkel
mesh_terms: D000336:Aerosols; D000818:Animals; D000881:Anthrax / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D001408:Bacillus anthracis / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D053474:Nod1 Signaling Adaptor Protein / Q000172:deficiency / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency / Q000276:immunology*; D013171:Spores, Bacterial / Q000276:immunology; D016019:Survival Analysis
chemical_list: D000336:Aerosols; D000907:Antibodies, Bacterial; D016207:Cytokines; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse