Abstract
Although precisely controlled innate immune response is governed by conserved cellular events in phylogenetically diverse hosts, the underlying molecular mechanisms by which this process is regulated against a multi-host pathogen remain unknown. Fusarium oxysporum is a model multi-host pathogen, known to be associated with neuronal stress in humans and vascular wilt in plants. The interaction between innate immune and neuronal pathways is the basis of many diverse biological responses. How these processes are coordinated in response to fungal disease is not well understood. Here, we show that F. oxysporum f. sp. ciceri causes neuronal stress and intestinal disintegration, ultimately leading to the death of Caenorhabditis elegans. To explore the regulatory framework of Fusarium-associated disease, we analysed the gene expression during infection, integrated temporal gene expression, and network analysis with genetic inactivation data in Caenorhabditis elegans. We identified 1024 genes showing significant changes in expression (corrected P-values <0.05) in response to Fusarium infection. Co-expression network analysis of our data identified prognostic genes related to disease progression. These genes were dynamically expressed in various neuronal and non-neuronal tissues exhibiting diverse biological functions, including cellular homeostasis, organ patterning, stress response, and lipid metabolism. The RNA-seq analysis further identified shared and unique signalling pathways regulated by DAF-16/FOXO and SIR-2.1 linking neuronal stress, which facilitates negative regulation of intestinal innate immunity. Genetic analysis revealed that GCY-5 in ASE functions upstream of DAF-16, whereas ASI-specific SRD-1 regulates behavioural immunity. Overall, our results indicate that a ubiquitous response occurs during Fusarium infection mediated by highly conserved regulatory components and pathways, which can be exploited further for the identification of disease-responsive genes conserved among animals and plants. Finally, this study provided a novel insight into cross-species immune signalling and may facilitate the discovery of cellular therapeutic targets for Fusarium-associated disease.
Highlights
Morbidity and mortality associated with fungal infections and emergence of resistant fungal strains necessitate the study of fungal pathogenesis and host innate immunity
Worms showed a high susceptibility to F. oxysporum f. sp. ciceri, as compared to F. oxysporum f. sp. methioli
Survivability of the worms grown on F. oxysporum f. sp. lycopersici was comparable to control worms grown on Escherichia coli OP50 (Figure 1a)
Summary
Morbidity and mortality associated with fungal infections and emergence of resistant fungal strains necessitate the study of fungal pathogenesis and host innate immunity. Evidences suggest that a common virulence mechanism exists for a wide array of pathogenic fungi with broad host ranges.[1] Several pathogens, including Fusarium, have the ability to infect both animals and plants.[2] It has emerged as the second most frequent mould causing invasive fungal infection in humans and exhibits a broad resistance to antifungal drugs.[3,4] It acts as an opportunistic invader causing allergies, sinusitis, and pulmonary infections in immunocompromised and immunocompetent patients.[4] Fusariuminduced neuronal stress and mycotoxicosis are considered as potential risk factors in humans and rats.[5,6] In plants, it causes vascular wilt, head blight, root rot, seedling blight, and foot rot diseases,[7,8,9] while Fusarium-mediated killing of Caenorhabditis elegans has recently been described.[10] Previously, cross-kingdom pathogenicity of F. oxysporum f. Cross-kingdom pathogenicity of F. oxysporum f. sp. lycopersici was investigated in mice to unravel the disease mechanism in plants and mammals.[11]
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