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Abstract
The nematode Caenorhabditis elegans has been extensively used as a model for the study of innate immune responses against bacterial pathogens. While it is well established that the worm mounts distinct transcriptional responses to different bacterial species, it is still unclear in how far it can fine-tune its response to different strains of a single pathogen species, especially if the strains vary in virulence and infection dynamics. To rectify this knowledge gap, we systematically analyzed the C. elegans response to two strains of Bacillus thuringiensis (Bt), MYBt18247 (Bt247) and MYBt18679 (Bt679), which produce different pore forming toxins (PFTs) and vary in infection dynamics. We combined host transcriptomics with cytopathological characterizations and identified both a common and also a differentiated response to the two strains, the latter comprising almost 10% of the infection responsive genes. Functional genetic analyses revealed that the AP-1 component gene jun-1 mediates the common response to both Bt strains. In contrast, the strain-specific response is mediated by the C. elegans GATA transcription factor ELT-2, a homolog of Drosophila SERPENT and vertebrate GATA4-6, and a known master regulator of intestinal responses in the nematode. elt-2 RNAi knockdown decreased resistance to Bt679, but remarkably, increased survival on Bt247. The elt-2 silencing-mediated increase in survival was characterized by reduced intestinal tissue damage despite a high pathogen burden and might thus involve increased tolerance. Additional functional genetic analyses confirmed the involvement of distinct signaling pathways in the C. elegans defense response: the p38-MAPK pathway acts either directly with or in parallel to elt-2 in mediating resistance to Bt679 infection but is not required for protection against Bt247. Our results further suggest that the elt-2 silencing-mediated increase in survival on Bt247 is multifactorial, influenced by the nuclear hormone receptors NHR-99 and NHR-193, and may further involve lipid metabolism and detoxification. Our study highlights that the nematode C. elegans with its comparatively simple immune defense system is capable of generating a differentiated response to distinct strains of the same pathogen species. Importantly, our study provides a molecular insight into the diversity of biological processes that are influenced by a single master regulator and jointly determine host survival after pathogen infection.
Highlights
In nature animal hosts are commonly exposed to different strains of a given pathogen species, which may vary in virulence factor expression and infection dynamics
We used the nematode C. elegans as a model to elucidate the common and, importantly, distinct defense responses directed at different strains of the same pathogen taxon, Bacillus thuringiensis (Bt), which vary in infection characteristics
Our work demonstrates that invertebrate defense responses against two different strains of the same pathogen species can be distinct, that they likely involve tolerance against one of the strains and are mediated by a single transcription factor as a central master switch
Summary
In nature animal hosts are commonly exposed to different strains of a given pathogen species, which may vary in virulence factor expression and infection dynamics. It is largely unknown how such variation between multiple pathogen strains of a given species affect the host’s first line of defense: the innate immune response. Only few studies directly tested how different strains of a pathogen affect the host immune response. Transcriptome analyses revealed striking differences in the host gene expression response to different genotypes of the trypanosome gut parasite Crithidia bombi, which vary in infectivity [12]. In the fruit fly Drosophila melanogaster, different genotypes of the parasitoid wasp Leptopilina boulardi, which differ in virulence, differentially affect cellular and humoral immune responses [13]
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