This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Loving, C. L.
Right arrow Articles by Merkel, T. J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Loving, C. L.
Right arrow Articles by Merkel, T. J.

 Previous Article  |  Next Article 

Infection and Immunity, October 2009, p. 4529-4537, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00563-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Nod1/Nod2-Mediated Recognition Plays a Critical Role in Induction of Adaptive Immunity to Anthrax after Aerosol Exposure{triangledown}

Crystal L. Loving,1,{dagger} Manuel Osorio,2 Yun-Gi Kim,3 Gabriel Nuñez,3 Molly A. Hughes,4 and Tod J. Merkel1*

Laboratory of Respiratory and Special Pathogens,1 Laboratory of Enteric and Sexually Transmitted Diseases, Division of Bacterial, Parasitic and Allergenic Products, CBER, FDA, Bethesda, Maryland,2 Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan,3 Division of Infectious Diseases, Department of Internal Medicine, University of Virginia Health Sciences System, Charlottesville, Virginia4

Received 20 May 2009/ Returned for modification 10 June 2009/ Accepted 10 July 2009

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-1β, 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.

* Corresponding author. Mailing address: Building 29, Room 418, 29 Lincoln Drive, Bethesda, MD 20892. Phone: (301) 496-5564. Fax: (301) 402-2776. E-mail: tod.merkel{at}fda.hhs.gov

{triangledown} Published ahead of print on 20 July 2009.

Editor: J. B. Bliska

{dagger} Present address: Respiratory Diseases of Livestock Research Unit, USDA/ARS/NADC, 2300 Dayton Avenue B13, Ames, IA 50010.

Infection and Immunity, October 2009, p. 4529-4537, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00563-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»