M Protein of Group a Streptococcus Plays an Essential Role in Inducing High Expression of A20 in Macrophages Resulting in the Downregulation of Inflammatory Response in Lung Tissue

Ma, Cuiqing; Gao, Xiaohan; Wu, Shu-Hui; Zhang, Ling; Wang, Jiachao; Zhang, Zhengzheng; Yao, Zhigang; Song, Xiaotian; Li, Wenjian; Wang, Xiurong; Hong, Feng; Wei, Lin

doi:10.3389/fcimb.2018.00131

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…The histology of the GAS-infected mouse lung tissue was analyzed using hematoxylin-eosin staining (H&E), as described previously ( 69 ). In brief, the mice were anesthetized using isoflurane in a biosafety cabinet.…”

Section: Methodsmentioning

confidence: 99%

Integrin α5β1, as a Receptor of Fibronectin, Binds the FbaA Protein of Group A Streptococcus To Initiate Autophagy during Infection

Wang

Meng

et al. 2020

mBio

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Group A Streptococcus (GAS), one of the most common extracellular pathogens, has been reported to invade epithelial and endothelial cells. Our results reveal that M1 GAS strain SF370 can be effectively eliminated by respiratory epithelial cells. Emerging evidence indicates that autophagy is an important strategy for nonphagocytes to eliminate intracellular bacteria. Upon pathogen recognition, cell surface receptors can directly trigger autophagy, which is a critical step in controlling infection. However, the mechanisms of how cells sense invading bacteria and use this information specifically to trigger autophagy remain unclear. In this study, we stimulated cells and infected mice with M and FbaA mutants of M1 GAS strain SF370 or with purified M and FbaA proteins (two critical surface structural proteins of GAS), and found that only FbaA protein was involved in autophagy induction. Furthermore, the FbaA protein induced autophagy independent of common pattern recognition receptors (such as Toll-like receptors); rather, it relies on binding to integrin α5β1 expressed on the cell surface, which is mediated by extracellular matrix protein fibronectin (Fn). The FbaA-Fn-integrin α5β1 complex activates Beclin-1 through the mTOR-ULK1–Beclin-1 pathway, which enables the Beclin-1/Vps34 complex to recruit Rab7 and, ultimately, to promote the formation of autophagosomes. By knocking down integrin α5β1, Fn, Atg5, Beclin-1, and ULK1 in Hep2 cells and deleting Atg5 or integrin α5β1 in mice, we reveal a novel role for integrin α5β1 in inducing autophagy. Our study demonstrates that integrin α5β1, through interacting with pathogen components, initiates effective host innate immunity against invading intracellular pathogens. IMPORTANCE Autophagy is generally considered a strategy used by the innate immune system to eliminate invasive pathogens through capturing and transferring them to lysosomes. Currently, researchers pay more attention to how virulence factors secreted by GAS regulate the autophagic process. Here, we provide the first evidence that the structural protein FbaA of M1 GAS strain SF370 is a potent inducer of autophagy in epithelial cells. Furthermore, we demonstrate that integrin α5β1 in epithelial cells in vitro and in vivo acts as a receptor to initiate the signaling for inducing autophagy by binding to FbaA of M1 GAS strain SF370 via Fn. Our study reveals the underlying mechanisms by which pathogens induce Fn-integrin α5β1 to trigger autophagy in a conserved pattern in epithelial cells.

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Section: Methodsmentioning

confidence: 99%

Integrin α5β1, as a Receptor of Fibronectin, Binds the FbaA Protein of Group A Streptococcus To Initiate Autophagy during Infection

Wang

Meng

et al. 2020

mBio

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“…An invasive disease is defined as the isolation of GAS from a normally sterile site of the body and it occurs when bacteria spread throughout the bloodstream, the cerebrospinal fluid, the lungs, and soft tissue [ 1 ]. A critical virulence factor is the M protein [ 2 , 3 ]. Invasive group A Streptococcus infection (iGAS) is a life-threatening condition, with high case fatality rates and high morbidity.…”

Section: Introductionmentioning

confidence: 99%

State of the Art of Invasive Group A Streptococcus Infection in Children: A Scoping Review of the Literature with a Focus on Predictors of Invasive Infection

Mariani,

Gentili,

Pulcinelli

et al. 2023

Children

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Currently, it remains unclear why some children develop invasive group A Streptococcus (iGAS) and how to manage this condition. Therefore, to explore available works in the literature, we performed a scoping review aiming to analyze the current literature on clinical presentation of different illnesses outcomes of iGAS, with a specific focus on predictors of invasive infection, including an assessment of the prodromal stages of the disease and the possible presence of previous non-invasive GAS infections in children that later developed iGAS. Methods: We conducted a systematic search on PubMed and SCOPUS of all pediatric studies reporting iGAS cases, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. For those studies in which multivariable analysis investigating iGAS risk factors was performed, a second review was performed and reported in detail. Results: A total of 209 studies were included. Five studies investigated risk factors for iGAS, the most relevant being varicella infection, chronic underlying illness, presence of the speC gene in GAS strains, acetaminophen and ibuprofen use, children nonwhite, living in low-income households, exposure to varicella at home, persistent high fever, having more than one other child in the home, and new use of NSAIDs. Although we observed a progressive increase in the number of papers published on this topic, no trials investigating the benefits of clindamycin or intravenous immunoglobulins were found and low-to-middle-income countries were found to be poorly represented in the current literature. Conclusions: Our scoping review highlights important gaps regarding several aspects of iGAS in children, including prodromic presentation and optimal treatment strategies. There is also little representation of low–middle-income countries. The current literature does not allow the performance of systematic reviews or meta-analyses, but this work should inform healthcare professionals, policy makers, and funding agencies on which studies to prioritize on this topic.

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Metagenomic shotgun sequencing reveals host species as an important driver of virome composition in mosquitoes

Thongsripong

Chandler

Kittayapong

et al. 2021

Sci Rep

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High-throughput nucleic acid sequencing has greatly accelerated the discovery of viruses in the environment. Mosquitoes, because of their public health importance, are among those organisms whose viromes are being intensively characterized. Despite the deluge of sequence information, our understanding of the major drivers influencing the ecology of mosquito viromes remains limited. Using methods to increase the relative proportion of microbial RNA coupled with RNA-seq we characterize RNA viruses and other symbionts of three mosquito species collected along a rural to urban habitat gradient in Thailand. The full factorial study design allows us to explicitly investigate the relative importance of host species and habitat in structuring viral communities. We found that the pattern of virus presence was defined primarily by host species rather than by geographic locations or habitats. Our result suggests that insect-associated viruses display relatively narrow host ranges but are capable of spreading through a mosquito population at the geographical scale of our study. We also detected various single-celled and multicellular microorganisms such as bacteria, alveolates, fungi, and nematodes. Our study emphasizes the importance of including ecological information in viromic studies in order to gain further insights into viral ecology in systems where host specificity is driving both viral ecology and evolution.

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M Protein of Group a Streptococcus Plays an Essential Role in Inducing High Expression of A20 in Macrophages Resulting in the Downregulation of Inflammatory Response in Lung Tissue

Cited by 4 publications

References 34 publications

Integrin α5β1, as a Receptor of Fibronectin, Binds the FbaA Protein of Group A Streptococcus To Initiate Autophagy during Infection

Integrin α5β1, as a Receptor of Fibronectin, Binds the FbaA Protein of Group A Streptococcus To Initiate Autophagy during Infection

State of the Art of Invasive Group A Streptococcus Infection in Children: A Scoping Review of the Literature with a Focus on Predictors of Invasive Infection

Metagenomic shotgun sequencing reveals host species as an important driver of virome composition in mosquitoes

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