Abstract
Hosts have developed diverse mechanisms to counter the pathogens they face in their natural environment. Throughout the plant and animal kingdoms, the up-regulation of antimicrobial peptides is a common response to infection. In C. elegans, infection with the natural pathogen Drechmeria coniospora leads to rapid induction of antimicrobial peptide gene expression in the epidermis. Through a large genetic screen we have isolated many new mutants that are incapable of upregulating the antimicrobial peptide nlp-29 in response to infection (i.e. with a Nipi or ‘no induction of peptide after infection’ phenotype). More than half of the newly isolated Nipi mutants do not correspond to genes previously associated with the regulation of antimicrobial peptides. One of these, nipi-4, encodes a member of a nematode-specific kinase family. NIPI-4 is predicted to be catalytically inactive, thus to be a pseudokinase. It acts in the epidermis downstream of the PKC∂ TPA-1, as a positive regulator of nlp antimicrobial peptide gene expression after infection. It also controls the constitutive expression of antimicrobial peptide genes of the cnc family that are targets of TGFß regulation. Our results open the way for a more detailed understanding of how host defense pathways can be molded by environmental pathogens.
Highlights
Pathogenic microorganisms represent one of the most ubiquitous and powerful sources of selection for higher eukaryotes including humans [1]
To characterize the molecular pathways that underpin antifungal innate immunity in C. elegans, we previously undertook a small-scale genetic screen for genes required for the induction of an antimicrobial peptides (AMPs) reporter gene after infection
We isolated and characterized 5 alleles that fall into 4 complementation groups. This provided a framework to understand the regulation of antimicrobial peptide expression in the C. elegans epidermis [39]
Summary
Pathogenic microorganisms represent one of the most ubiquitous and powerful sources of selection for higher eukaryotes including humans [1]. Different pathogens have specific natural host tropisms, sometimes broad, as in the case of Pseudomonas aeruginosa [2,3], and in other cases, such as HIV, very narrow. Part of this tropism reflects the divergent mechanisms of host resistance, as exemplified by cultivar-specific resistance in plants [4]. In contrast to most other animal species, nematodes, including Caenorhabditis elegans, have lost NF-kB, a key transcription factor in immunity [5,6,7]. Studying the interaction of C. elegans with its natural pathogens sheds light on NF-kBindependent defense pathways
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