Article

Specificity of the innate immune system and diversity of C-type lectin domain (CTLD) proteins in the nematode Caenorhabditis elegans.

Department of Animal Evolutionary Ecology, Zoological Institute, University of Tuebingen, Auf der Morgenstelle 28, 72076 Tuebingen, Germany.
Immunobiology (Impact Factor: 3.18). 02/2008; 213(3-4):237-50. DOI: 10.1016/j.imbio.2007.12.004
Source: PubMed

ABSTRACT The nematode Caenorhabditis elegans has become an important model for the study of innate immunity. Its immune system is based on several signaling cascades, including a Toll-like receptor, three mitogen-activated protein kinases (MAPK), one transforming growth factor-beta (TGF-beta), the insulin-like receptor (ILR), and the programmed cell death (PCD) pathway. Furthermore, it also involves C-type lectin domain- (CTLD) containing proteins as well as several classes of antimicrobial effectors such as lysozymes. Almost all components of the nematode immune system have homologs in other organisms, including humans, and are therefore likely of ancient evolutionary origin. At the same time, most of them are part of a general stress response, suggesting that they only provide unspecific defense. In the current article, we re-evaluate this suggestion and explore the level of specificity in C. elegans innate immunity, i.e. the nematode's ability to mount a distinct defense response towards different pathogens. We draw particular attention to the CTLD proteins, which are abundant in the nematode genome (278 genes) and many of which show a pathogen-specific response during infection. Specificity may also be achieved through the differential activation of antimicrobial genes, distinct functions of the immunity signaling cascades as well as signal integration across pathways. Taken together, our evaluation reveals high potential for immune specificity in C. elegans that may enhance the nematode's ability to fight off pathogens.

Full-text

Available from: Erich Bornberg-Bauer, Apr 23, 2014
2 Followers
 · 
218 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: C-type lectins are among the most significant pattern recognition receptors (PRRs) found in invertebrate. They are a class of carbohydrate-binding proteins that can recognize specific sugar moieties on the surface of pathogens. In the present study, a novel C-type lecitn (termed MjLectin) from kuruma shrimp Marsupenaeus japonicus was identified. The full-length cDNA of MjLectin was 1 245 bp with a 1 011 bp open reading frame (ORF) that encoded a polypeptide of 336 amino acid residues. MjLectin consisted of two tandemly arrayed carbohydrate-recognition domains (CRDs), unlike other reported M. japonicus C-type lectins with only one CRD. It showed a high similarity to other shrimp dual-CRD lectins. Among the Ca2+-binding Site 2, the tripeptide motif dictating the carbohydrate binding specificity was exhibited as a rare mutant LPN (Leu134-Pro135-Asn136) in CRD1 and a traditional EPN (Glu299-Pro300-Asn301) in CRD2, respectively. MjLectin showed a specific expression pattern in both tissue and cellular levels, for its mRNA transcript was mainly expressed in the F-cells of the hepatopancreas. After white spot syndrome virus (WSSV) challenge (3.6×108 virions/μL), the expression of MjLectin in the hepatopancreas was up-regulated significantly at 48 h (P
    Acta Oceanologica Sinica -English Edition- 02/2015; 34(2):74-83. DOI:10.1007/s13131-015-0623-x · 0.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Caenorhabditis elegans can be infected by a plethora of pathogens, most of them are also pathogenic for humans. Consequently, the nematode has emerged as a powerful surrogate host to model microbial human infectious diseases in a non-vertebrate, for the study of innate immunity and host –pathogen interactions. Signaling cascades are well investigated that face bacterial or fungal pathogens. We analyzed the downstream processes of these cascades, i.e. the differential expression of effector and regulatory molecules due to a microbial challenge with a pathogenic strain of the bacterium Bacillus thuringiensis (Bt) in comparison to a non-pathogenic Bt strain. The protein abundance profile of the nematode was studied by quantitative proteomics using iTRAQ labeling and 2D-LC–MS analysis. We developed (i) a novel method for the preparation of defined C. elegans samples; (ii) a pooling strategy for fractions in 2D-LC separation schemes; and (iii) an isobaric labeling scheme reducing the number of necessary LC–MS experiments.More than 3,600 proteins were quantified, 288 of which showed altered abundances, implicating protein classes such as lectins, lysozymes, and transthyretin-like proteins to be involved in the nematode innate immune defense. A number of gene products previously only identified by transcriptomic profiling could be verified at the protein level. Moreover, several other protein classes such as proteases, proteins related to autophagy and apoptosis, structural proteins, and proteins involved in chromatin organization were detected.The results provide an overview of the physiological response towards a pathogen at protein level in the important model organism C. elegans, giving insights into highly complex host–pathogen interactions.Biological significanceThis study identified system-wide effects of Bt intoxication on C. elegans at protein level, expanding the catalogue of immune effectors potentially acting towards the pathogen, and provide verification for numerous gene products implicated in previous transcriptomic studies. The data present evidence in support of both a general defense response as well as a specific reaction against the Bt toxin within the nematode. The described findings will also contribute to a deeper understanding of host–microbe interaction in other organisms, including humans, and may provide key information that touches far reaching aspects of coevolutionary processes.
    Journal of Proteomics 10/2014; 113. DOI:10.1016/j.jprot.2014.09.027 · 3.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pathogen infection can activate multiple signaling cascades that ultimately alter the abundance of molecules in cells. This change can be measured both at the transcript and protein level. Studies analyzing the immune response at both levels are, however, rare. Here, we compare transcriptome and proteome data generated after infection of the nematode and model organism Caenorhabditis elegans with the Gram-positive pathogen Bacillus thuringiensis. Our analysis revealed a high overlap between abundance changes of corresponding transcripts and gene products, especially for genes encoding C-type lectin domain-containing proteins, indicating their particular role in worm immunity. We additionally identified a unique signature at the proteome level, suggesting that the C. elegans response to infection is shaped by changes beyond transcription. Such effects appear to be influenced by AMP-activated protein kinases (AMPKs), which may thus represent previously unknown regulators of C. elegans immune defense. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
    Developmental & Comparative Immunology 02/2015; 18(1). DOI:10.1016/j.dci.2015.02.010 · 3.71 Impact Factor