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Molecular and Cellular Biology, August 2007, p. 5544-5553, Vol. 27, No. 15
0270-7306/07/$08.00+0     doi:10.1128/MCB.02070-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Specificity and Complexity of the Caenorhabditis elegans Innate Immune Response{triangledown} ,{dagger}

Scott Alper,1,2* Sandra J. McBride,3 Brad Lackford,1 Jonathan H. Freedman,3,4 and David A. Schwartz1,2

Laboratory of Respiratory Biology,1 Laboratory of Molecular Toxicology, National Institutes of Environmental Health Sciences, NIH, 111 T.W. Alexander Dr., Durham, North Carolina 27709,3 Duke University Medical Center, Durham, North Carolina 27707,2 Nicholas School of the Environment and Earth Sciences, Duke University, Durham, North Carolina 277084

Received 6 November 2006/ Returned for modification 16 January 2007/ Accepted 16 May 2007

In response to infection, Caenorhabditis elegans produces an array of antimicrobial proteins. To understand the C. elegans immune response, we have investigated the regulation of a large, representative sample of candidate antimicrobial genes. We found that all these putative antimicrobial genes are expressed in tissues exposed to the environment, a position from which they can ward off infection. Using RNA interference to inhibit the function of immune signaling pathways in C. elegans, we found that different immune response pathways regulate expression of distinct but overlapping sets of antimicrobial genes. We also show that different bacterial pathogens regulate distinct but overlapping sets of antimicrobial genes. The patterns of genes induced by pathogens do not coincide with any single immune signaling pathway. Thus, even in this simple model system for innate immunity, striking specificity and complexity exist in the immune response. The unique patterns of antimicrobial gene expression observed when C. elegans is exposed to different pathogens or when different immune signaling pathways are perturbed suggest that a large set of yet to be identified pathogen recognition receptors (PRRs) exist in the nematode. These PRRs must interact in a complicated fashion to induce a unique set of antimicrobial genes. We also propose the existence of an "antimicrobial fingerprint," which will aid in assigning newly identified C. elegans innate immunity genes to known immune signaling pathways.

* Corresponding author. Mailing address: Laboratory of Respiratory Biology, NIEHS, 111 T.W. Alexander Dr., MD B3-08, Durham, NC 27709. Phone: (919) 541-4377. Fax: (919) 541-9825. E-mail: alpers{at}niehs.nih.gov

{triangledown} Published ahead of print on 25 May 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, August 2007, p. 5544-5553, Vol. 27, No. 15
0270-7306/07/$08.00+0     doi:10.1128/MCB.02070-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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