VEGF-Mediated Augmentation of Autophagic and Lysosomal Activity in Endothelial Cells Defends against Intracellular Streptococcus pyogenes

Lu, Shiou-Ling; Omori, Hiroko; Zhou, Yi; Lin, Yee‐Shin; Liu, Ching-Chuan; Wu, Jiunn-Jong; Noda, Tetsuji

doi:10.1128/mbio.01233-22

Cited by 11 publications

(7 citation statements)

References 59 publications

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“…The soluble receptors ICAM1, VCAM1 have shown their potential as biomarkers [prognostic, diagnostic ( 25 )] for inflammatory responses in a variety of diseases. VEGF, an angiogenetic factor, has been reported to play a crucial role in bacterial pathogen-induced inflammatory responses ( 26 ) including in the immune defense against Streptococcus pyogenes ( 27 ). Also noteworthy is the fact that S. aureus triggers VEGF in mast cells suggesting that the increased presence of VEGF in the blood could serve as a marker for bacterial infections ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Profiling of serum factors associated with Staphylococcus aureus skin and soft tissue infections as a foundation for biomarker identification

Bergmann-Leitner,

Millar,

Duncan

et al. 2023

Front. Immunol.

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BackgroundPeople living in close quarters, such as military trainees, are at increased risk for skin and soft tissue infections (SSTI), especially those caused by methicillin-resistant Staphylococcus aureus (MRSA). The serum immune factors associated with the onset of SSTI are not well understood.MethodsWe conducted a longitudinal study of SSTIs, enrolling US Army trainees before starting military training and following up for 14 weeks. Samples were collected on Day 0, 56, and 90. Serum chemokines and cytokines among 16 SSTI cases and 51 healthy controls were evaluated using an electro-chemiluminescence based multiplex assay platform.ResultsOf 54 tested cytokines, 12 were significantly higher among SSTI cases as compared to controls. Among the cases, there were correlations between factors associated with vascular injury (i.e., VCAM-1, ICAM-1, and Flt1), the angiogenetic factor VEGF, and IL-10. Unsupervised machine learning (Principal Component Analysis) revealed that IL10, IL17A, C-reactive protein, ICAM1, VCAM1, SAA, Flt1, and VGEF were indicative of SSTI.ConclusionThe study demonstrates the power of immunoprofiling for identifying factors predictive of pre-illness state of SSTI thereby identifying early stages of an infection and individuals susceptible to SSTI.

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Section: Discussionmentioning

confidence: 99%

Profiling of serum factors associated with Staphylococcus aureus skin and soft tissue infections as a foundation for biomarker identification

Bergmann-Leitner,

Millar,

Duncan

et al. 2023

Front. Immunol.

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“…It has been proposed that vascular endothelial growth factor (VEGF) expressed in endothelial cells may promote antimicrobial response against S. pyogenes infection, as observed in vitro with human endothelial cells increasing lysosomal biogenesis and function and overall bacterial xenophagy against S. pyogenes through the activation of TFEB and its downstream genes (e.g., ATPV6 and LAMP1), and in vivo with VEGF treatment significantly increasing subject survival rate (Lu et al, 2022). Moreover, patients with severe invasive disease (sepsis, bacteremia, necrotizing fasciitis, and TSS) exhibit significantly lower serum levels of VEGF compared to those with non-invasive disease (Lu et al, 2022). Also relating to host immune response, TLR signaling plays an important role in early immune reactions against S. pyogenes.…”

Section: Host Factorsmentioning

confidence: 99%

“…Sitkiewicz and Musser (2017) Vascular endothelial growth factor Administration improves survival. Lu et al (2022) Pattern recognition receptor TLR13 Knockout mice exhibit limited macrophage IL-6 and NO2 production. Hafner et al (2019) CXCL-1, CXC motif chemokine ligand 1; DSL, C-terminal disulfide loop; GSH, glutathione; HIF1α, hypoxia inducible factor 1 subunit α; IL, interleukin; K1-CPS, K1 serotype capsule polysaccharide; MDA, malondialdehyde; MPO, myeloperoxidase; NLRP3, NOD-like receptor family pyrin domain-containing 3; PAD2, peptidyl arginine deiminase type 2; PGE2, prostaglandin E2; PLGA, poly(lactic-co-glycolic acid); PTX3, pentraxin 3; ROS, reactive oxygen species; SCFA, short-chain fatty acids; SOD, superoxide dismutase; TLR13, toll-like receptor 13; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.…”

Section: Spy_1476mentioning

confidence: 99%

Novel evidence on sepsis-inducing pathogens: from laboratory to bedside

Gatica,

Fuentes,

Rivera-Asín

et al. 2023

Front. Microbiol.

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Sepsis is a life-threatening condition and a significant cause of preventable morbidity and mortality globally. Among the leading causative agents of sepsis are bacterial pathogens Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pyogenes, along with fungal pathogens of the Candida species. Here, we focus on evidence from human studies but also include in vitro and in vivo cellular and molecular evidence, exploring how bacterial and fungal pathogens are associated with bloodstream infection and sepsis. This review presents a narrative update on pathogen epidemiology, virulence factors, host factors of susceptibility, mechanisms of immunomodulation, current therapies, antibiotic resistance, and opportunities for diagnosis, prognosis, and therapeutics, through the perspective of bloodstream infection and sepsis. A list of curated novel host and pathogen factors, diagnostic and prognostic markers, and potential therapeutical targets to tackle sepsis from the research laboratory is presented. Further, we discuss the complex nature of sepsis depending on the sepsis-inducing pathogen and host susceptibility, the more common strains associated with severe pathology and how these aspects may impact in the management of the clinical presentation of sepsis.

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“…[ 26 ] Intracellular bacteria are then released and possibly reabsorbed by other phagocytes leading to a continuous cycle of lysis and uptake maintaining the population of intracellular bacteria. Alternatively, the release of such viable bacteria from phagocytes may also invade nonprofessional phagocytes, such as epithelial cells, [ 27 ] endothelial cells, [ 28 ] osteoblasts, [ 29 ] and fibroblasts. [ 30 ] In contrast to professional phagocytes, these nonprofessional phagocytes lack sufficient capacity to defend against bacteria.…”

Section: Host Cells and Intracellular Bacteriamentioning

confidence: 99%

Targeted Drug Delivery Systems for Eliminating Intracellular Bacteria

Feng

Chittò

Moriarty

et al. 2022

Macromolecular Bioscience

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The intracellular survival of pathogenic bacteria requires a range of survival strategies and virulence factors. These infections are a significant clinical challenge, wherein treatment frequently fails because of poor antibiotic penetration, stability, and retention in host cells. Drug delivery systems (DDSs) are promising tools to overcome these shortcomings and enhance the efficacy of antibiotic therapy. In this review, the classification and the mechanisms of intracellular bacterial persistence are elaborated. Furthermore, the systematic design strategies applied to DDSs to eliminate intracellular bacteria are also described, and the strategies used for internalization, intracellular activation, bacterial targeting, and immune enhancement are highlighted. Finally, this overview provides guidance for constructing functionalized DDSs to effectively eliminate intracellular bacteria.

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VEGF-Mediated Augmentation of Autophagic and Lysosomal Activity in Endothelial Cells Defends against Intracellular Streptococcus pyogenes

Abstract: Sepsis caused by Streptococcus pyogenes is a life-threatening condition. Blood vessel endothelial cells should serve as a barrier to infection, although we recently reported that endothelial cells allow intracellular GAS proliferation due to defective xenophagy.

Cited by 11 publications

References 59 publications

Profiling of serum factors associated with Staphylococcus aureus skin and soft tissue infections as a foundation for biomarker identification

Profiling of serum factors associated with Staphylococcus aureus skin and soft tissue infections as a foundation for biomarker identification

Novel evidence on sepsis-inducing pathogens: from laboratory to bedside

Targeted Drug Delivery Systems for Eliminating Intracellular Bacteria

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