The conceptual foundations of innate immunity: Taking stock 30 years later

Immunity, Год журнала: 2024, Номер 57(4), С. 613 - 631

Опубликована: Апрель 1, 2024

SummaryWhile largely neglected over decades during which adaptive immunity captured most of the attention, innate immune mechanisms have now become central to our understanding immunology. Innate provides first barrier infection in vertebrates, and it is sole mechanism host defense invertebrates plants. also plays a critical role maintaining homeostasis, shaping microbiota, disease contexts such as cancer, neurodegeneration, metabolic syndromes, aging. The emergence field has led an expanded view system, no longer restricted vertebrates instead concerns all metazoans, plants, even prokaryotes. study given rise new concepts language. Here, we review history definition core immunity, discussing their value fruitfulness long run.

Язык: Английский

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A systematic framework for understanding the microbiome in human health and disease: from basic principles to clinical translation

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Сен. 23, 2024

Язык: Английский

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Host control of the microbiome: Mechanisms, evolution, and disease

Science, Год журнала: 2024, Номер 385(6706)

Опубликована: Июль 18, 2024

Many species, including humans, host communities of symbiotic microbes. There is a vast literature on the ways these microbiomes affect hosts, but here we argue for an increased focus how hosts their microbiomes. Hosts exert control over symbionts through diverse mechanisms, immunity, barrier function, physiological homeostasis, and transit. These mechanisms enable to shape ecology evolution generate natural selection microbial traits that benefit host. Our result from perpetual tension between symbiont evolution, can leverage host's evolved abilities regulate microbiota prevent treat disease. The study will be central our ability both understand manipulate microbiotas better health.

Язык: Английский

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The role of animal hosts in shaping gut microbiome variation

Philosophical Transactions of the Royal Society B Biological Sciences, Год журнала: 2024, Номер 379(1901)

Опубликована: Март 18, 2024

Millions of years co-evolution between animals and their associated microbial communities have shaped diversified the nature relationship. Studies continue to reveal new layers complexity in host–microbe interactions, fate which depends on a variety different factors, ranging from neutral processes environmental factors local dynamics. Research is increasingly integrating ecosystem-based approaches, metagenomics mathematical modelling disentangle individual contribution ecological microbiome evolution. Within this framework, host are known be among dominant drivers composition animal species. However, extent they shape assembly evolution remains unclear. In review, we summarize our understanding how drive these dynamics conserved vary across taxa. We conclude by outlining key avenues for research highlight need implementation modifications existing theory fully capture host-associated microbiomes. This article part theme issue ‘Sculpting microbiome: determine respond colonization’.

Язык: Английский

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The antimicrobial peptide database is 20 years old: Recent developments and future directions

Protein Science, Год журнала: 2023, Номер 32(10)

Опубликована: Сен. 11, 2023

In 2023, the Antimicrobial Peptide Database (currently available at https://aps.unmc.edu) is 20-years-old. The timeline for APD expansion in peptide entries, classification methods, search functions, post-translational modifications, binding targets, and mechanisms of action antimicrobial peptides (AMPs) has been summarized our previous Protein Science paper. This article highlights new database additions findings. To facilitate development to combat drug-resistant pathogens, re-annotating data antibacterial activity (active, inactive, uncertain), toxicity (hemolytic nonhemolytic AMPs), salt tolerance (salt sensitive insensitive). Comparison respective desired undesired AMP groups produces knowledge design. Our unification AMPs from six life kingdoms into "natural AMPs" enabled first comparison with globular or transmembrane proteins. Due dominance amphipathic helical disulfide-linked peptides, cysteine, glycine, lysine natural are much more abundant than those include predicted by machine learning, a "predicted" group created. Remarkably, averaged amino acid composition located between lower bound upper synthetic peptides. Synthetic current APD, highest cationic hydrophobic percentages, mostly designed varying degrees optimization. Hence, accumulated over 20 years have laid foundation learning prediction. We discuss future directions discovery. It anticipated that will continue play role research education.

Язык: Английский

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Evolutionary immunology to explore original antiviral strategies

Philosophical Transactions of the Royal Society B Biological Sciences, Год журнала: 2024, Номер 379(1901)

Опубликована: Март 18, 2024

Over the past 25 years, field of evolutionary developmental biology (evo–devo) has used genomics and genetics to gain insight on mechanisms underlying evolution morphological diversity animals. Evo–devo exploits key that conserved toolkits development (e.g. Hox genes) are in animals produce genetic novelties provide adaptation a new environment. Like development, immunity is forged by interactions with environment, namely microbial world. Yet, when it comes study immune defence invertebrates, interest primarily focuses evolutionarily molecules also present humans. Here, focusing antiviral immunity, we argue genes not humans represent an unexplored resource for discovery strategies. We review recent findings cGAS-STING pathway explain how cyclic dinucleotides produced cGAS-like receptors may be investigate portfolio broad range species. This will set stage evo–immuno approaches, exploiting investment defences made metazoans over hundreds millions years evolution. article part theme issue ‘Sculpting microbiome: host factors determine respond colonization’.

Язык: Английский

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Suppression of Drosophila antifungal immunity by a parasite effector via blocking GNBP3 and GNBP-like 3, the dual receptors for β-glucans

Cell Reports, Год журнала: 2024, Номер 43(1), С. 113642 - 113642

Опубликована: Янв. 1, 2024

The tactics used by animal pathogens to combat host immunity are largely unclear. Here, we report the depiction of virulence-required effector Tge1 deployed entomopathogen Metarhizium robertsii suppress Drosophila antifungal immunity. can target both GNBP3 and GNBP-like 3 (GL3), latter bind β-glucans like GNBP3, whereas glucan binding receptors be attenuated Tge1. As opposed surveillance GL3 is inducible in depending on Toll pathway via a positive feedback loop mechanism. Losses genes result deregulations protease cascade, Spätzle maturation, antimicrobial gene expressions upon fungal challenges. Fly survival assays confirm that plays more essential role than combating infections. In addition evidencing gene-for-gene interactions between fungi insects, our data advance insights into

Язык: Английский

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Novel technologies uncover novel ‘anti’-microbial peptides in Hydra shaping the species-specific microbiome

Philosophical Transactions of the Royal Society B Biological Sciences, Год журнала: 2024, Номер 379(1901)

Опубликована: Март 18, 2024

The freshwater polyp Hydra uses an elaborate innate immune machinery to maintain its specific microbiome. Major components of this toolkit are conserved Toll-like receptor (TLR)-mediated pathways and species-specific antimicrobial peptides (AMPs). Our study harnesses advanced technologies, such as high-throughput sequencing machine learning, uncover a high complexity the 's AMPs repertoire. Functional analysis reveals that these against diverse members microbiome expressed in spatially controlled pattern. Notably, outer epithelial layer, produced mainly neurons. neuron-derived secreted directly into glycocalyx, habitat for symbiotic bacteria, display selectivity spatial restriction expression. In endodermal contrast, cells produce abundance different including arminin hydramacin families, while gland secrete kazal-type protease inhibitors. Since layer lines gastric cavity devoid we assume endodermally protect from intruding pathogens. conclusion, employs complex set distinct tissue layers cell types combat pathogens stable organized This article is part theme issue ‘Sculpting microbiome: how host factors determine respond microbial colonization’.

Язык: Английский

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

Philosophical Transactions of the Royal Society B Biological Sciences, Год журнала: 2024, Номер 379(1901)

Опубликована: Март 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’.

Язык: Английский

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Functional Antimicrobial Peptide-loaded 3D Scaffolds for Infected Bone Defect Treatment with AI and Multidimensional Printing

Materials Horizons, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Infection is the most prevalent complication of fractures, particularly in open and often leads to severe consequences.

Язык: Английский

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