RESUMO
The increasing prevalence of drug-resistant Escherichia coli (E. coli) resulting from the excessive utilization of antibiotics necessitates the immediate exploration of alternative approaches to counteract pathogenic E. coli. Phages, with their unique antibacterial mechanisms, are considered promising candidates for treating bacterial infections. Herein, we isolated a lytic Escherichia phage Tequatrovirus YZ2 (phage YZ2), which belongs to the genus Tequatrovirus. The genome of phage YZ2 consists of 168,356 base pairs with a G + C content of 35.34% and 269 putative open reading frames (ORFs). Of these, 146 ORFs have been annotated as functional proteins associated with nucleotide metabolism, structure, transcription, DNA replication, translation, and lysis. In the mouse model of a skin wound infected by E. coli, phage YZ2 therapy significantly promoted the wound healing. Furthermore, histopathological analysis revealed reductions in IL-1ß and TNF-α and increased VEGF levels, indicating the potential of phages as effective antimicrobial agents against E. coli infection.
Assuntos
Infecções por Escherichia coli , Escherichia coli , Genoma Viral , Infecção dos Ferimentos , Animais , Escherichia coli/virologia , Escherichia coli/genética , Camundongos , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/virologia , Infecção dos Ferimentos/tratamento farmacológico , Fases de Leitura Aberta , Colífagos/genética , Colífagos/fisiologia , Terapia por Fagos , Modelos Animais de Doenças , Cicatrização , Composição de Bases , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismoRESUMO
Erythrocytes capture pathogens in circulation and present them to antigen-presenting cells (APCs) in the spleen. Senescent or apoptotic erythrocytes are physiologically eliminated by splenic APCs in a non-inflammatory manner as to not induce an immune reaction, while damaged erythrocytes tend to induce immune activation. The distinct characteristics of erythrocytes in their lifespan or different states inspire the design of targeting splenic APCs for vaccine delivery. Specifically, normal or damaged erythrocyte-driven immune targeting can induce antigen-specific immune activation, whereas senescent or apoptotic erythrocytes can be tailored to achieve antigen-specific immune tolerance. Recent studies have revealed the potential of erythrocyte-based vaccine delivery; however, there is still no in-depth review to describe the latest progress. This review summarizes the characteristics, different immune functions, and diverse vaccine delivery behaviors and biomedical applications of erythrocytes in different states. This review aims to contribute to the rational design and development of erythrocyte-based vaccine delivery systems for treating various infections, tumors, inflammatory diseases, and autoimmune diseases.
Assuntos
Sistemas de Liberação de Medicamentos , Vacinas , Eritrócitos , Técnicas de Transferência de Genes , ImunomodulaçãoRESUMO
BACKGROUND: Diabetic wound healing remains a challenge because of its susceptibility to drug-resistant bacterial infection and its persistent proinflammatory state. Switching from proinflammatory M1 macrophages (Mφs) to proregenerative M2 dominant Mφs in a timely manner accelerates wound healing by coordinating inflammatory, proliferative, and angiogenic processes. METHODS: We propose a sequential photothermal antibacterial and subsequent M2 Mφ polarization strategy based on nanofibers (NFs) consisting of polydopamine (PDA) coating on curcumin (Cur) nanocrystals to treat Methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wounds. RESULTS: The PDA/Cur NFs showed excellent photothermal conversion and antibacterial effects due to the PDA shell under laser irradiation, consequently resulting in the release of the inner Cur with the ability to promote cell proliferation and reinforce the M2 Mφ phenotype in vitro. In vivo studies on MRSA-infected diabetic wounds showed that PDA/Cur NFs not only inhibited MRSA infection but also accelerated the wound regeneration process. Furthermore, the NFs displayed the ability to promote the M2 Mφ phenotype with enhanced collagen deposition, angiogenesis, and cell proliferation. CONCLUSION: Overall, the NFs displayed great potential as promising therapeutics for healing infected diabetic wounds through a sequential photothermal antibacterial and M2 Mφ polarization strategy.
Assuntos
Antibacterianos , Complicações do Diabetes , Nanofibras , Infecções Estafilocócicas , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/microbiologia , Humanos , Macrófagos/efeitos dos fármacos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Nanofibras/química , Nanofibras/uso terapêutico , Células RAW 264.7 , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologiaRESUMO
An appropriate delivery system can improve the immune effects of antigens against various infections or tumors. Antigen-presenting cells (APCs) are specialized to capture and process antigens in vivo, which link the innate and adaptive immune responses. Functionalization of vaccine delivery systems with targeting moieties to APCs is a promising strategy for provoking potent immune responses. Additionally, the internalization and intracellular distribution of antigens are closely related to the initiation of downstream immune responses. With a deeper understanding of the intracellular microenvironment and the mechanisms of antigen presentation, vehicles designed to respond to endogenous and external stimuli can modulate antigen processing and presentation pathways, which are critical to the types of immune response. Here, an overview of extracellular targeting delivery of antigens to APCs and intracellular stimulus-responsiveness strategies is provided, which might be helpful for the rational design of vaccine delivery systems.