Immune responses to human fungal pathogens and therapeutic prospects

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(7), P. 433 - 452

Published: Jan. 4, 2023

Language: Английский

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Photochemical Strategies toward Precision Targeting against Multidrug-Resistant Bacterial Infections

ACS Nano, Journal Year: 2024, Volume and Issue: 18(22), P. 14085 - 14122

Published: May 22, 2024

Infectious diseases pose a serious threat and substantial economic burden on global human public health security, especially with the frequent emergence of multidrug-resistant (MDR) bacteria in clinical settings. In response to this urgent need, various photobased anti-infectious therapies have been reported lately. This Review explores discusses several photochemical targeted antibacterial therapeutic strategies for addressing bacterial infections regardless their antibiotic susceptibility. contrast conventional therapies, these approaches facilitate precise targeting pathogenic and/or infectious microenvironments, effectively minimizing toxicity mammalian cells surrounding healthy tissues. The highlighted include photodynamic therapy, photocatalytic photothermal endogenous pigments-based photobleaching polyphenols-based photo-oxidation therapy. comprehensive exploration aims offer updated information development effective, convenient, safe, alternative counter growing MDR future.

Language: Английский

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Linking vaccine adjuvant mechanisms of action to function

Science Immunology, Journal Year: 2025, Volume and Issue: 10(104)

Published: Feb. 14, 2025

Vaccines deliver an immunogen in a manner designed to safely provoke immune response, leading the generation of memory T and B cells long-lived antibody-producing plasma cells. Adjuvants play critical role vaccines by controlling how system is exposed providing inflammatory cues that enable productive priming. However, mechanisms action underlying adjuvant function at molecular, cell, tissue levels are diverse often poorly understood. Here, we review current understanding adjuvants used subunit protein/polysaccharide mRNA vaccines, discuss where possible these link downstream effects on identify knowledge gaps will be important fill order continued development more effective for challenging pathogens such as HIV emerging threats.

Language: Английский

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The advances of adjuvants in mRNA vaccines

npj Vaccines, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 26, 2023

The remarkable success of messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has propelled the rapid development this vaccination technology in recent years. Over last three decades, numerous studies have shown considerable potential mRNA that elicit protective immune responses pathogens or cancers preclinical clinical trials. These effective usually contain specific adjuvants to obtain desired effect. Vaccine traditionally are immunopotentiators bind pattern recognition receptors (PRRs) innate cells increase magnitude achieve qualitative alteration responses, finally enhancing efficacy vaccines. Generally, necessary parts competent According existing literature, can be broadly classified into categories: 1) with self-adjuvant characteristics, 2) components delivery system, and 3) exogenous immunostimulants. This review summarizes types used provides a comprehensive understanding molecular mechanisms by which exert their functions

Language: Английский

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Resolving adjuvant mode of action to enhance vaccine efficacy

Current Opinion in Immunology, Journal Year: 2022, Volume and Issue: 77, P. 102229 - 102229

Published: June 29, 2022

Adjuvants are a miscellaneous range of molecules and materials that can enhance the magnitude, functionality, breadth durability immune responses. Despite multiplicity compounds with adjuvant properties, less than dozen in clinical use vaccines against infectious diseases. While many factors have contributed to their slow development, among major challenges high safety efficacy standards set by current adjuvants human our limited understanding how mediate effects. This review outlines why it is so difficult elucidate mechanism action, highlights areas require in-depth research discusses recent advancements revitalising development. It hoped fuller sensing, signalling function will facilitate design promote sustained protective immunity challenging bacterial viral pathogens.

Language: Английский

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Adjuvant physiochemistry and advanced nanotechnology for vaccine development

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(15), P. 5172 - 5254

Published: Jan. 1, 2023

This review provides an introduction of basic principles adjuvanted human vaccines in clinics and summarizes emerging nanotechnology adjuvants vaccine development against cancer infectious diseases.

Language: Английский

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Rewilding of laboratory mice enhances granulopoiesis and immunity through intestinal fungal colonization

Science Immunology, Journal Year: 2023, Volume and Issue: 8(84)

Published: June 23, 2023

The paucity of blood granulocyte populations such as neutrophils in laboratory mice is a notable difference between this model organism and humans, but the cause species-specific unclear. We previously demonstrated that released into seminatural environment, referred to rewilding, display an increase granulocytes associated with expansion fungi gut microbiota. Here, we find tonic signals from fungal colonization induce sustained granulopoiesis through mechanism distinct emergency granulopoiesis, leading prolonged circulating promotes immunity. Fungal after either rewilding or oral inoculation Candida albicans induced persistent myeloid progenitors bone marrow. This conferred greater long-term protection bloodstream infection by gram-positive bacteria than trained immune response evoked transient exposure cell wall component β-glucan. Consequently, introducing may restore aspects leukocyte development provide better for humans free-living mammals are constantly exposed environmental fungi.

Language: Английский

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Circular RNA vaccines with long-term lymph node-targeting delivery stability after lyophilization induce potent and persistent immune responses

mBio, Journal Year: 2023, Volume and Issue: 15(1)

Published: Dec. 11, 2023

messenger RNA (mRNA) vaccines are a key technology in combating existing and emerging infectious diseases. However, the inherent instability of mRNA nonspecificity lipid nanoparticle-encapsulated (LNP) delivery systems result need for cold storage relatively short-duration immune response to vaccines. Herein, we develop novel vaccine form circRNAs encapsulated LNPs, circular structure enhances their stability. Lyophilization is considered most effective method long-term preservation this process may irreversible damage nanoparticles, particularly potential disruption targeting modifications on LNPs. During selection lymph node-targeting ligands, found that LNPs modified with mannose maintained physical properties almost unchanged after lyophilization. Additionally, specificity immunogenicity remained unaffected. In contrast, even addition cryoprotectants such as sucrose, were impaired, leading an obvious decrease immunogenicity. This be attributed protective role surface during Freshly prepared lyophilized mLNP-circRNA elicited comparable responses both rabies virus model SARS-CoV-2 model. Our data demonstrated elicit robust while improving stability lyophilization, no compromise tissue specificity. Therefore, mannose-modified LNP-circRNA represent promising design strategy.

Language: Английский

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Histone demethylases in the regulation of immunity and inflammation

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: June 23, 2023

Abstract Pathogens or danger signals trigger the immune response. Moderate response activation removes pathogens and avoids excessive inflammation tissue damage. Histone demethylases (KDMs) regulate gene expression play essential roles in numerous physiological processes by removing methyl groups from lysine residues on target proteins. Abnormal of KDMs is closely associated with pathogenesis various inflammatory diseases such as liver fibrosis, lung injury, autoimmune diseases. Despite becoming exciting targets for diagnosing treating these diseases, role enzymes regulation still unclear. Here, we review underlying mechanisms through which immune-related pathways responses. In addition, also discuss future applications inhibitors

Language: Английский

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Candida albicans N-Linked Mannans Potentiate the Induction of Trained Immunity via Dectin-2

The Journal of Infectious Diseases, Journal Year: 2024, Volume and Issue: 230(3), P. 768 - 777

Published: March 6, 2024

Abstract The interaction between the Candida albicans cell wall and pattern recognition receptors is crucial for initiation of host immune responses, which, ultimately, contribute to clearance this pathogenic fungus. In present study, we investigate ability C. mannans modulate response induce innate memory (also termed trained immunity). Using mutants that are defective in or lack mannosyl residues, show alterations mannosylation affect cytokine strongly reduce secretion T-cell–derived cytokines. Subsequently, demonstrate branching N-linked mannan, but not O-linked essential potentiate induction immunity, a process mediated by dectin 2. conclusion, mannan needed, addition β-glucans, an effective immunity albicans.

Language: Английский

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