When the microbiome shapes the host: immune evolution implications for infectious disease

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2024, Volume and Issue: 379(1901)

Published: March 18, 2024

The microbiome includes both ‘mutualist’ and ‘pathogen’ microbes, regulated by the same innate immune architecture. A major question has therefore been: how do hosts prevent pathogenic infections while maintaining beneficial microbes? One idea suggests can selectively activate immunity upon infection, but not mutualist colonization. Another posits that attack pathogens, mutualists. Here I review evolutionary principles of microbe recognition activation, reflect on newly observed effector–microbe specificity perhaps supporting latter idea. Recent work in Drosophila found a surprising importance for single antimicrobial peptides combatting specific ecologically relevant microbes. developing picture these effectors have evolved this purpose. Other defence responses like reactive oxygen species bursts also be uniquely effective against Signals other model systems including nematodes, Hydra , oysters, mammals, suggest may fundamental principle host–pathogen interactions. propose stems from weaknesses microbes themselves: if intrinsic weaknesses, evolve exploit those weaknesses. define host–microbe relationship as ‘the Achilles evolution’. Incorporating view helps interpret why some interactions develop coevolutionary framework (e.g. Red Queen dynamics), or one-sided response. This clarification should valuable to better understand behind host susceptibilities infectious diseases. article is part theme issue ‘Sculpting microbiome: factors determine respond microbial colonization’.

Language: Английский

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Ageing leads to reduced specificity of antimicrobial peptide responses in Drosophila melanogaster

Proceedings of the Royal Society B Biological Sciences, Journal Year: 2022, Volume and Issue: 289(1987)

Published: Nov. 16, 2022

Evolutionary theory predicts a late-life decline in the force of natural selection, possibly leading to deregulations immune system. A potential outcome such is inability produce specific immunity against target pathogens. We tested this possibility by infecting multiple Drosophila melanogaster lines (with bacterial pathogens) across age groups, where either individual or different combinations Imd- and Toll-inducible antimicrobial peptides (AMPs) were deleted using CRISPR gene editing. show high degree non-redundancy pathogen-specificity AMPs young flies: some cases, even single AMP could confer complete resistance. However, ageing led drastic reductions specificity pathogens, warranting action Imd Toll pathways. Moreover, use diverse lacked survival benefits accompanied costs post-infection. These features also sexually dimorphic: females required larger repertoire than males but extracted equivalent benefits. Finally, age-specific expansion AMP-repertoire was with ageing-induced downregulation negative-regulators pathway damage renal function post-infection, as poorly regulated immunity. Overall, we highlight potentially non-adaptive role producing less-specific responses, sexes

Language: Английский

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IMD-mediated innate immune priming increases Drosophila survival and reduces pathogen transmission

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 23, 2023

Abstract Invertebrates lack the immune machinery underlying vertebrate-like acquired immunity. However, in many insects past infection by same pathogen can ‘prime’ response, resulting improved survival upon reinfection. Here, we investigated generality, specificity and mechanistic basis of innate priming fruit fly Drosophila melanogaster when infected with gram-negative bacterial Providencia rettgeri . We find that response to P. is a long-lasting pathogen-specific response. further explore epidemiological consequences it has potential curtail transmission reducing shedding spread. The enhanced individuals previously exposed non-lethal inoculum coincided transient decrease loads, provide strong evidence effect requires IMD-responsive antimicrobial-peptide Diptericin-B fat body. Further, show while Diptericin B main effector clearance, not sufficient for priming, which regulation IMD peptidoglycan recognition proteins. This work underscores plasticity complexity invertebrate responses infection, providing novel experimental effects on population-level outcomes.

Language: Английский

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When the microbiome shapes the host: immune evolution implications for infectious disease

Published: Oct. 24, 2023

The microbiome includes both “mutualist” and “pathogen” microbes, regulated by the same innate immune architecture. A major question has therefore been: how do hosts prevent pathogenic infections while maintaining beneficial microbes? One idea suggests can selectively activate immunity upon infection, but not mutualist colonisation. Another posits that attack pathogens, mutualists. Here I review evolutionary principles of microbe recognition activation, reflect on newly-observed effector-microbe specificity perhaps supporting latter idea.Recent work in Drosophila found a surprising importance for single antimicrobial peptides combatting specific ecologically-relevant microbes. developing picture these effectors have evolved this purpose. Other defence responses like ROS bursts also be uniquely effective against Signals other model systems including nematodes, Hydra, oysters, mammals, suggest may fundamental principle host-pathogen interactions. propose stems from weaknesses microbes themselves: if intrinsic weaknesses, evolve exploit those weaknesses. define host-microbe relationship as “the Achilles evolution.” Incorporating view helps interpret why some interactions develop coevolutionary framework (e.g. Red Queen dynamics), or one-sided response. This clarification should valuable to better understand behind host susceptibilities infectious diseases.

Language: Английский

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Fly immunity comes of age: The utility of Drosophila as a model for studying variation in immunosenescence

Frontiers in Aging, Journal Year: 2022, Volume and Issue: 3

Published: Oct. 4, 2022

OPINION article Front. Aging, 04 October 2022Sec. Genetics, Genomics and Epigenomics of Aging Volume 3 - 2022 | https://doi.org/10.3389/fragi.2022.1016962

Language: Английский

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A suite of selective pressures supports the maintenance of alleles of a Drosophila immune peptide

Published: Oct. 29, 2024

The innate immune system provides hosts with a crucial first line of defense against pathogens. While genes are often among the fastest evolving in genome, Drosophila , antimicrobial peptides (AMPs) notable exceptions. Instead, AMPs may be under balancing selection, such that over evolutionary timescales multiple alleles maintained populations. In this study, we focus on peptide Diptericin A, which has segregating amino acid polymorphism associated differential survival after infection Gram-negative bacteria Providencia rettgeri . A also helps control opportunistic gut infections by common microbes, especially those Lactobacillus plantarum addition to genotypic effects immunity, see strong sex-specific most prominent flies without functional diptericin To further characterize differences microbiomes between different genotypes, used 16S metagenomics look at microbiome composition. We both lab reared and wild caught for our sequencing looked overall composition as well abundance individual bacterial families. Overall, find homozygous one allele better equipped survive systemic from P. but general have shorter lifespans being fed commensals. Our results suggest possible mechanism maintenance genetic variation through complex interactions sex, microbiome.

Language: Английский

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A suite of selective pressures supports the maintenance of alleles of aDrosophilaimmune peptide

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 21, 2023

Abstract The innate immune system provides hosts with a crucial first line of defense against pathogens. While genes are often among the fastest evolving in genome, Drosophila , antimicrobial peptides (AMPs) notable exceptions. Instead, AMPs may be under balancing selection, such that over evolutionary timescales multiple alleles maintained populations. In this study, we focus on peptide Diptericin A, which has segregating amino acid polymorphism associated differential survival after infection Gram-negative bacteria Providencia rettgeri . A also helps control opportunistic gut infections by common microbes, especially those Lactobacillus plantarum addition to genotypic effects immunity, see strong sex-specific most prominent flies without functional diptericin To further characterize differences microbiomes between different genotypes, used 16S metagenomics look at microbiome composition. We both lab reared and wild caught for our sequencing looked overall composition as well abundance individual bacterial families. Overall, find homozygous one allele better equipped survive systemic from P. but general have shorter lifespans being fed commensals. Our results suggest possible mechanism maintenance genetic variation through complex interactions sex, microbiome.

Language: Английский

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A suite of selective pressures supports the maintenance of alleles of a Drosophila immune peptide

Published: Oct. 27, 2023

The innate immune system provides hosts with a crucial first line of defense against pathogens. While genes are often among the fastest evolving in genome, Drosophila , antimicrobial peptides (AMPs) notable exceptions. Instead, AMPs may be under balancing selection, such that over evolutionary timescales multiple alleles maintained populations. In this study, we focus on peptide Diptericin A, which has segregating amino acid polymorphism associated differential survival after infection Gram-negative bacteria Providencia rettgeri . A also helps control opportunistic gut infections by common microbes, especially those Lactobacillus plantarum addition to genotypic effects immunity, see strong sex-specific most prominent flies without functional diptericin To further characterize differences microbiomes between different genotypes, used 16S metagenomics look at microbiome composition. We both lab reared and wild caught for our sequencing looked overall composition as well abundance individual bacterial families. Overall, find homozygous serine better equipped survive systemic from P. but general arginine have longer lifespan being fed commensals. Our results suggest possible mechanism maintenance genetic variation through complex interactions sex, microbiome.

Language: Английский

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A suite of selective pressures supports the maintenance of alleles of a Drosophila immune peptide

Published: Oct. 27, 2023

The innate immune system provides hosts with a crucial first line of defense against pathogens. While genes are often among the fastest evolving in genome, Drosophila , antimicrobial peptides (AMPs) notable exceptions. Instead, AMPs may be under balancing selection, such that over evolutionary timescales multiple alleles maintained populations. In this study, we focus on peptide Diptericin A, which has segregating amino acid polymorphism associated differential survival after infection Gram-negative bacteria Providencia rettgeri . A also helps control opportunistic gut infections by common microbes, especially those Lactobacillus plantarum addition to genotypic effects immunity, see strong sex-specific most prominent flies without functional diptericin To further characterize differences microbiomes between different genotypes, used 16S metagenomics look at microbiome composition. We both lab reared and wild caught for our sequencing looked overall composition as well abundance individual bacterial families. Overall, find homozygous one allele better equipped survive systemic from P. but general have shorter lifespans being fed commensals. Our results suggest possible mechanism maintenance genetic variation through complex interactions sex, microbiome.

Language: Английский

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