Schulenburg, H., Hoeppner, M. P., Weiner, J. & Bornberg-Bauer, E. Specificity of the innate immune system and diversity of C-type lectin domain (CTLD) proteins in the nematode Caenorhabditis elegans. Immunobiology 213, 237-250

Department of Animal Evolutionary Ecology, Zoological Institute, University of Tuebingen, Auf der Morgenstelle 28, 72076 Tuebingen, Germany.
Immunobiology (Impact Factor: 3.04). 02/2008; 213(3-4):237-50. DOI: 10.1016/j.imbio.2007.12.004
Source: PubMed


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.

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Available from: Erich Bornberg-Bauer, Apr 23, 2014
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    • "C. elegans has no adaptive immune system and the animal is believed to depend purely upon the secretion and action of antimicrobial molecules, including lysozymes (Schulenburg and Boehnisch, 2008), lectins (Schulenburg et al., 2008), caenopores (Roeder et al., 2010) and antibacterial factors (Kato et al., 2002). The primary route and major site of infection for S. aureus in a C. elegans model is through the intestine (Sifri et al., 2003). "
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    ABSTRACT: Amidst growing concerns over the spread of antibiotic-resistant Staphylococcus aureus strains, the identification of alternative therapeutic molecules has become paramount. Previously, we utilized a Caenorhabditis elegans-S. aureus screening platform to identify potential anti-infective agents from a collection of natural extracts and synthetic compounds. One of the hits obtained from the screen was the aqueous extract of Orthosiphon stamineus leaves (UE-12) that enhanced the survival of infected nematodes without interfering with bacterial growth. In this study, we used a fluorescent transgenic reporter strain and observed that the repressed expression of the lys-7 defense gene in infected nematodes was restored in the presence of UE-12. Analysis of a selected panel of PMK-1 and DAF-16-regulated transcripts and loss-of-function mutants in these pathways indicates that the protective role of UE-12 is mediated via the p38 MAP kinase and insulin-like signaling pathways. Further analysis of a panel of known bioactive compounds of UE-12 proposed eupatorin (C18H16O7) as the possible candidate active molecule contributing to the anti-infective property of UE-12. Taken together, these findings strongly suggest that the O. stamineus leaf extract is a promising anti-infective agent that confers an advantage in survival against S. aureus infection by modulating the immune response of the infected host.
    Biology Open 06/2014; 3(7). DOI:10.1242/bio.20148334 · 2.42 Impact Factor
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    • "ignaling pathways , hlh - 30 regulated an ' ' antimi - crobial ' ' component of the host response ( Figures 3C and 3D ) including genes that encode proteins with proposed or demon - strated antimicrobial activity , such as lysozymes , C - type lectins , antimicrobial peptides , and ferritin ( Boehnisch et al . , 2011 ; Hoeckendorf et al . , 2012 ; Schulenburg et al . , 2008 ; Simonsen et al . , 2011 ; Tarr , 2012 ) . We verified hlh - 30 - dependent induction of 14 genes in this group ( Figures 4A – 4D ; Figure S3A ) , demonstrating that HLH - 30 is necessary for induction of the antimicrobial response . Furthermore , expression was restored by complementation with HLH - 30 : : GFP for a majority of genes "
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    Immunity 05/2014; 40:1. DOI:10.1016/j.immuni.2014.05.002 · 21.56 Impact Factor
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    • "Once host resources are made available, the spores germinate and proliferate vegetatively until cells sporulate. Both antagonists show potential for specific interactions: Bt strains show high specificity against nematodes, including C. elegans (Wei et al., 2003; Schulenburg and Ewbank, 2004; Schulenburg and Müller, 2004; Schulte et al., 2010), and C. elegans expresses specific immune reactions toward different pathogens (Alper et al., 2007; Wong et al., 2007; Schulenburg et al., 2008). "
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