Natural Infection of C. elegans by an Oomycete Reveals a New Pathogen-Specific Immune Response

Abstract

In its natural habitat, the nematode Caenorhabditis elegans encounters a plethora of other organisms, including many that are pathogenic [1, 2]. The study of interactions between C. elegans and various pathogens has contributed to characterizing key mechanisms of innate immunity [2-4]. However, how C. elegans recognizes different pathogens to mount pathogen-specific immune responses remains still largely unknown [3, 5-8]. Expanding the range of known C. elegans-infecting pathogens and characterizing novel pathogen-specific immune responses are key steps toward answering this question. We report here that the oomycete Myzocytiopsis humicola is a natural pathogen of C. elegans, and we describe its infection strategy. We identify a new host immune response to pathogen exposure that involves induction of members of a previously uncharacterized gene family encoding chitinase-like (CHIL) proteins. We demonstrate that this response is highly specific against M. humicola and antagonizes the infection. We propose that CHIL proteins may diminish the ability of the oomycete to infect by hindering pathogen attachment to the host cuticle. This work expands our knowledge of natural eukaryotic pathogens of C. elegans and introduces a new pathosystem to address how animal hosts recognize and respond to oomycete infections.

Antagonistic paralogs control a switch between growth and pathogen resistance inC. elegans

“…Notably these genes do not include the well-characterized neuropeptide nlp defense genes, although they do include many of the pals genes. A more recently described natural pathogen of C. elegans is Myzocytiopsis humicola , which is an oomycete that also infects through the epidermis and causes a lethal infection [19]. Here as well, pals-22/25 regulate a significant number of genes in common with those induced by M. humicola infection, including the chi tinase-like ‘ chil’ genes that promote defense against this pathogen (S10 Table).…”

“…Here as well, pals-22/25 regulate a significant number of genes in common with those induced by M. humicola infection, including the chi tinase-like ‘ chil’ genes that promote defense against this pathogen (S10 Table). Interestingly, these chil genes, like the pals genes, are species-specific [8, 19].…”

“…Interestingly, we found that pals-22/25 regulate expression of genes induced not only by natural intestinal pathogens but also of genes induced by natural epidermal pathogens, such as the oomycete species M. humicola. M. humicola induces expression of chil- gene family, and genetic analysis shows these genes promote defense against M. humicola [19]. Notably, we identified pals-22/25 in independent forward genetic screens for regulators of chil-27 and found that they regulate expression of this defense gene in the epidermis.…”

Balancing selection of the Intracellular Pathogen Response in natural Caenorhabditis elegans populations

“…Three antiviral responses are known of which RNA interference (RNAi) and uridylation both target viral RNA for degradation [7,[9][10][11]. The third response, the so-called Intracellular Pathogen Response (IPR), is thought to relieve proteotoxic stress from the infection by the OrV and other intracellular pathogens [12][13][14][15]. The 80 genes involved in the IPR pathway are controlled by pals-22 and pals-25 that function as a molecular switch between growth and antiviral defense.…”

Systematic Identification of Housekeeping Genes Possibly Used as References in Caenorhabditis elegans by Large-Scale Data Integration

“…Gene expression analysis in this model organism constitutes a powerful tool to discover new roles for different types of molecules. Traditionally, a set of housekeeping genes encoding actin (act-1) [7,8], tubulin (tba-1) [9][10][11], glyceraldehyde-3-phosphate dehydrogenase (gpd-2) [12,13], translation initiation factor 3C (eif-3.C) [14,15], calsequestrin (csq-1) [13,16], Rho GTPase (cdc-42) [17][18][19][20], and peroxisomal membrane protein related (pmp-3) [18,21] were thought to be appropriate reference genes for the normalization of gene expression in C. elegans. However, some reports indicated that the transcription levels of these conserved reference genes may be changed under different conditions, such as developmental stages, drug treatments, and hypoxia [22,23].…”