A polymorphism in npr-1 is a behavioral determinant of pathogen susceptibility in C. elegans - PubMed (original) (raw)

A polymorphism in npr-1 is a behavioral determinant of pathogen susceptibility in C. elegans

Kirthi C Reddy et al. Science. 2009.

Abstract

The nematode Caenorhabditis elegans responds to pathogenic bacteria with conserved innate immune responses and pathogen avoidance behaviors. We investigated natural variation in C. elegans resistance to pathogen infection. With the use of quantitative genetic analysis, we determined that the pathogen susceptibility difference between the laboratory wild-type strain N2 and the wild isolate CB4856 is caused by a polymorphism in the npr-1 gene, which encodes a homolog of the mammalian neuropeptide Y receptor. We show that the mechanism of NPR-1-mediated pathogen resistance is through oxygen-dependent behavioral avoidance rather than direct regulation of innate immunity. For C. elegans, bacteria represent food but also a potential source of infection. Our data underscore the importance of behavioral responses to oxygen levels in finding an optimal balance between these potentially conflicting cues.

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Figures

Fig. 1

Fig. 1

The enhanced pathogen susceptibility of CB4856 is caused by the 215F allele of npr-1. A. Fraction alive versus time for N2 (orange) and CB4856 (blue) fed PA14 using standard assays (18). Means from 27 independent experiments for each strain are shown. B. Logarithm of the odds ratio (LOD) score for linkage between LT50 and 1454 single nucleotide polymorphims (SNPs) in 126 recombinant inbred lines showing one major quantitative trait locus on LGX. Dotted and solid lines show 5 and 0.1% genome-wide significance levels, respectively, determined from 1000 permutations. C. Fraction alive versus time for N2 (orange), CB4856 (blue), the npr-1 loss-of-function mutant ky13 (red), a complementation test between npr-1(ky13) derived from the N2 background and npr-1 derived from the CB4856 background (green), and rescue of the npr-1(ky13) allele (yellow).

Fig. 2

Fig. 2

_npr-1_-mediated behaviors determine the susceptibility of C. elegans to PA14. A. Fraction alive versus time for N2 (orange) and CB4856 (blue) fed PA14 on standard plates (solid lines) and big lawn plates (dotted lines). B. Fraction alive versus time for N2 (orange), CB4856 (blue), and the npr-1 loss-of-function allele ad609 (red) at 21% oxygen (solid lines) and 10% oxygen (dotted lines).

Fig. 3

Fig. 3

_npr-1_-mediated behaviors cause increased exposure to bacteria. Differential interference contrast and fluorescence microscopy of N2, CB4856, and npr-1(ad609) animals fed GFP-labeled PA14 for 24 hours on a standard lawn (A to C) or fed a 50:1 mixture of unlabeled PA14 and 0.2 μm fluorescent beads (D to F) or on a big lawn of GFP-labeled PA14 (G to I).

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