scholarly journals Antagonistic fungal enterotoxins intersect at multiple levels with host innate immune defences

PLoS Genetics ◽  
2021 ◽  
Vol 17 (6) ◽  
pp. e1009600
Author(s):  
Xing Zhang ◽  
Benjamin W. Harding ◽  
Dina Aggad ◽  
Damien Courtine ◽  
Jia-Xuan Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fungal Pathogen ◽  
Cell Biology ◽  
Innate Immune ◽  
Pathogen Virulence ◽  
Defence Gene Expression ◽  
Multiple Levels ◽  
Peptide Gene ◽  
Surveillance Mechanism ◽  
Immune Defences

Animals and plants need to defend themselves from pathogen attack. Their defences drive innovation in virulence mechanisms, leading to never-ending cycles of co-evolution in both hosts and pathogens. A full understanding of host immunity therefore requires examination of pathogen virulence strategies. Here, we take advantage of the well-studied innate immune system of Caenorhabditis elegans to dissect the action of two virulence factors from its natural fungal pathogen Drechmeria coniospora. We show that these two enterotoxins have strikingly different effects when expressed individually in the nematode epidermis. One is able to interfere with diverse aspects of host cell biology, altering vesicle trafficking and preventing the key STAT-like transcription factor STA-2 from activating defensive antimicrobial peptide gene expression. The second increases STA-2 levels in the nucleus, modifies the nucleolus, and, potentially as a consequence of a host surveillance mechanism, causes increased defence gene expression. Our results highlight the remarkably complex and potentially antagonistic mechanisms that come into play in the interaction between co-evolved hosts and pathogens.

scholarly journals Antagonistic fungal enterotoxins intersect at multiple levels with host innate immune defences

2020 ◽  
Author(s):  
Xing Zhang ◽  
Benjamin Harding ◽  
Dina Aggad ◽  
Damien Courtine ◽  
Jia-Xuan Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fungal Pathogen ◽  
Cell Biology ◽  
Innate Immune ◽  
Pathogen Virulence ◽  
Defence Gene Expression ◽  
Multiple Levels ◽  
Peptide Gene ◽  
Surveillance Mechanism ◽  
Immune Defences

ABSTRACTAnimals and plants need to defend themselves from pathogen attack. Their defences drive innovation in virulence mechanisms, leading to never-ending cycles of co-evolution in both hosts and pathogens. A full understanding of host immunity therefore requires examination of pathogen virulence strategies. Here, we take advantage of the well-studied innate immune system of Caenorhabditis elegans to dissect the action of two virulence factors from its natural fungal pathogen Drechmeria coniospora. We show that these two enterotoxins have strikingly different effects when expressed individually in the nematode epidermis. One is able to interfere with diverse aspects of host cell biology, altering vesicle trafficking and preventing the key STAT-like transcription factor STA-2 from activating defensive antimicrobial peptide gene expression. The second, potentially as a consequence of a host surveillance mechanism, increases STA-2 levels in the nucleus, modifies the nucleolus, and causes increased defence gene expression. Our results highlight the remarkably complex and potentially antagonistic mechanisms that come into play in the interaction between co-evolved hosts and pathogens.

scholarly journals Modulatory upregulation of an insulin peptide gene by different pathogens in C. elegans

2017 ◽  
Author(s):  
Song-Hua Lee ◽  
Shizue Omi ◽  
Nishant Thakur ◽  
Clara Taffoni ◽  
Jérôme Belougne ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Signaling ◽  
Kinase Inhibitor ◽  
Innate Immune ◽  
Immune Genes ◽  
C Elegans ◽  
Intestinal Infections ◽  
Innate Immune Genes ◽  
Peptide Gene ◽  
Complex Manner

ABSTRACTWhen an animal is infected, its innate immune response needs to be tightly regulated across tissues and coordinated with other aspects of organismal physiology. Previous studies with Caenorhabditis elegans have demonstrated that insulin-like peptide genes are differentially expressed in response to different pathogens. They represent prime candidates for conveying signals between tissues upon infection. Here, we focused on one such gene, ins-11 and its potential role in mediating cross-tissue regulation of innate immune genes. While diverse bacterial intestinal infections can trigger the up-regulation of ins-11 in the intestine, we show that epidermal infection with the fungus Drechmeria coniospora triggers an upregulation of ins-11 in the epidermis. Using the Shigella virulence factor OpsF, a MAP kinase inhibitor, we found that in both cases, ins-11 expression is controlled cell autonomously by p38 MAPK, but via distinct transcription factors, STA-2/STAT in the epidermis and HLH-30/TFEB in the intestine. We established that ins-11, and the insulin signaling pathway more generally, are not involved in the regulation of antimicrobial peptide gene expression in the epidermis. The up-regulation of ins-11 in the epidermis does, however, affect intestinal gene expression in a complex manner, and has a deleterious effect on longevity. These results support a model in which insulin signaling, via ins-11, contributes to the coordination of the organismal response to infection, influencing the allocation of resources in an infected animal.

scholarly journals Functional Characterization of a Novel Promoter Element Required for an Innate Immune Response in Drosophila

2003 ◽  
Vol 23 (22) ◽  
pp. 8272-8281 ◽  
Author(s):  
Hanna Uvell ◽  
Ylva Engström
Keyword(s):  
Gene Expression ◽  
Antimicrobial Peptide ◽  
Functional Characterization ◽  
Binding Activity ◽  
Innate Immune ◽  
Site Directed Mutagenesis ◽  
Promoter Element ◽  
Peptide Gene ◽  
Inducible Genes

ABSTRACT Innate immune reactions are crucial processes of metazoans to protect the organism against overgrowth of faster replicating microorganisms. Drosophila melanogaster is a precious model for genetic and molecular studies of the innate immune system. In response to infection, the concerted action of a battery of antimicrobial peptides ensures efficient killing of the microbes. The induced gene expression relies on translocation of the Drosophila Rel transcription factors Relish, Dif, and Dorsal to the nucleus where they bind to κB-like motifs in the promoters of the inducible genes. We have identified another putative promoter element, called region 1 (R1), in a number of antimicrobial peptide genes. Site-directed mutagenesis of the R1 site diminished Cecropin A1 (CecA1) expression in transgenic Drosophila larvae and flies. Infection of flies induced a nuclear R1-binding activity that was unrelated to the κB-binding activity in the same extracts. Although the R1 motif was required for Rel protein-mediated CecA1 expression in cotransfection experiments, our data argue against it being a direct target for the Drosophila Rel proteins. We propose that the R1 and κB motifs are targets for distinct regulatory complexes that act in concert to promote high levels of antimicrobial peptide gene expression in response to infection.

Physiology and metabolism of fungal pathogens

2017 ◽  
Author(s):  
Neil A.R. Gow ◽  
Alistair J.P. Brown
Keyword(s):  
Fungal Pathogen ◽  
Fungal Pathogens ◽  
Regulatory Networks ◽  
Innate Immune ◽  
Essential Nutrients ◽  
Immune Defences

The metabolism and physiology of an invading fungal pathogen determine the outcome of its interaction with the host. The pathogen must be able to assimilate nutrients to grow and colonize diverse host niches. Meanwhile, the host attempts to restrict this growth by withholding some essential nutrients, by imposing stresses, and by inducing innate immune defences. These interactions involve complex regulatory networks that ultimately dictate the equilibrium between pathogen killing and the establishment of commensal or pathogenic associations.

scholarly journals Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Katherine R. Dobbs ◽  
Paula Embury ◽  
Emmily Koech ◽  
Sidney Ogolla ◽  
Stephen Munga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Young Adults ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Innate Immune ◽  
Inflammatory Gene Expression ◽  
Cpg Sites ◽  
Age Related ◽  
Adults And Children

Abstract Background Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

scholarly journals Time-resolved transcriptional profiling of Trichinella-infected murine myocytes helps to elucidate host–pathogen interactions in the muscle stage

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiaoxiang Hu ◽  
Xiaolei Liu ◽  
Chen Li ◽  
Yulu Zhang ◽  
Chengyao Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Biology ◽  
Trichinella Spiralis ◽  
Expression Patterns ◽  
Muscle Cells ◽  
Host Cells ◽  
Initial Reaction ◽  
Global Changes ◽  
Mammalian Skeletal Muscle ◽  
Time Resolved

Abstract Background Parasites of the genus Trichinella are the pathogenic agents of trichinellosis, which is a widespread and severe foodborne parasitic disease. Trichinella spiralis resides primarily in mammalian skeletal muscle cells. After invading the cells of the host organism, T. spiralis must elude or invalidate the host’s innate and adaptive immune responses to survive. It is necessary to characterize the pathogenesis of trichinellosis to help to prevent the occurrence and further progression of this disease. The aims of this study were to elucidate the mechanisms of nurse cell formation, pathogenesis and immune evasion of T. spiralis, to provide valuable information for further research investigating the basic cell biology of Trichinella-infected muscle cells and the interaction between T. spiralis and its host. Methods We performed transcriptome profiling by RNA sequencing to identify global changes at 1, 3, 7, 10 and 15 days post-infection (dpi) in gene expression in the diaphragm after the parasite entered and persisted within the murine myocytes; the mice were infected by intravenous injection of newborn larvae. Gene expression analysis was based on the alignment results. Differentially expressed genes (DEGs) were identified based on their expression levels in various samples, and functional annotation and enrichment analysis were performed. Results The most extensive and dynamic gene expression responses in host diaphragms were observed during early infection (1 dpi). The number of DEGs and genes annotated in the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases decreased significantly in the infected mice compared to the uninfected mice at 3 and 7 dpi, suddenly increased sharply at 10 dpi, and then decreased to a lower level at 15 dpi, similar to that observed at 3 and 7 dpi. The massive initial reaction of the murine muscle cells to Trichinella infection steadied in the later stages of infection, with little additional changes detected for the remaining duration of the studied process. Although there were hundreds of DEGs at each time point, only 11 genes were consistently up- or downregulated at all 5 time points. Conclusions The gene expression patterns identified in this study can be employed to characterize the coordinated response of T. spiralis-infected myocytes in a time-resolved manner. This comprehensive dataset presents a distinct and sensitive picture of the interaction between host and parasite during intracellular infection, which can help to elucidate how pathogens evade host defenses and coordinate the biological functions of host cells to survive in the mammalian environment.

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