4.8 Article

Human Enteric α-Defensin 5 Promotes Shigella Infection by Enhancing Bacterial Adhesion and Invasion

期刊

IMMUNITY
卷 48, 期 6, 页码 1233-+

出版社

CELL PRESS
DOI: 10.1016/j.immuni.2018.04.014

关键词

-

资金

  1. Program 985 of Xi'an Jiaotong University
  2. Natural Science Foundation of China [31401211, 31770146]
  3. National Institutes of Health [R01GM106710, R01CA219150, R37AI032738]

向作者/读者索取更多资源

Shigella is a Gram-negative bacterium that causes bacillary dysentery worldwide. It invades the intestinal epithelium to elicit intense inflammation and tissue damage, yet the underlying mechanisms of its host selectivity and low infectious inoculum remain perplexing. Here, we report that Shigella coopts human alpha-defensin 5 (HD5), a host defense peptide important for intestinal homeostasis and innate immunity, to enhance its adhesion to and invasion of mucosal tissues. HD5 promoted Shigella infection in vitro in a structure-dependent manner. Shigella, commonly devoid of an effective host-adhesion apparatus, preferentially targeted HD5 to augment its ability to colonize the intestinal epithelium through interactions with multiple bacterial membrane proteins. HD5 exacerbated infectivity and Shigella-induced pathology in a culture of human colorectal tissues and three animal models. Our findings illuminate how Shigella exploits innate immunity by turning HD5 into a virulence factor for infection, unveiling a mechanism of action for this highly proficient human pathogen.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Biochemistry & Molecular Biology

Human intelectin-2 (ITLN2) is selectively expressed by secretory Paneth cells

Eric B. Nonnecke, Patricia A. Castillo, Malin E. Johansson, Edward J. Hollox, Bo Shen, Bo Lonnerdal, Charles L. Bevins

Summary: This study investigates the differences between ITLN2 and ITLN1 in terms of their structure and expression characteristics. It reveals that ITLN2 is a highly abundant Paneth cell-specific product in the small intestine, and its expression is downregulated in Crohn's disease. ITLN2 mRNA expression is undetectable in control colon tissue, but metaplastic Paneth cells express ITLN2 in both ulcerative colitis and colonic Crohn's disease.

FASEB JOURNAL (2022)

Article Chemistry, Multidisciplinary

A Tumor-Targeting Metal-Organic Nanoparticle Constructed by Dynamic Combinatorial Chemistry toward Accurately Redressing Carcinogenic Wnt Cascade

Tianya Liu, Jin Yan, Chenchen He, Weiming You, Fang Ma, Zhuo Chang, Yong Li, Suxia Han, Wangxiao He, Wenjia Liu

Summary: Targeted therapy and immunotherapy have transformed cancer treatment, but face challenges of side effects and limited response. Novel nanoscale infinite coordination polymers offer a feasible strategy for tumor targeting and immune sensitization. MOICP, constructed through a one-pot self-assembled strategy, shows promising results in inhibiting Wnt signaling and enhancing immunotherapy effectiveness in cancer models.
Article Cell Biology

A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection

Guillaume Beaudoin-Bussieres, Yaozong Chen, Irfan Ullah, Jeremie Prevost, William D. Tolbert, Kelly Symmes, Shilei Ding, Mehdi Benlarbi, Shang Yu Gong, Alexandra Tauzin, Romain Gasser, Debashree Chatterjee, Dani Vezina, Guillaume Goyette, Jonathan Richard, Fei Zhou, Leonidas Stamatatos, Andrew T. McGuire, Hughes Charest, Michel Roger, Edwin Pozharski, Priti Kumar, Walther Mothes, Pradeep D. Uchil, Marzena Pazgier, Andres Finzi

Summary: Emerging evidence suggests that both neutralizing and Fc-mediated effector functions of antibodies are important for protection against SARS-CoV-2. A non-neutralizing antibody, CV3-13, with potent Fc-mediated effector functions, was found to bind to a specific epitope of the SARS-CoV-2 spike from a unique angle. In mouse experiments, the Fc-enhanced version of CV3-13 delayed virus spread, neuroinvasion, and death, and the combination of Fc-enhanced CV3-13 with a neutralizing antibody completely protected mice from lethal SARS-CoV-2 infection.

CELL REPORTS (2022)

Article Cell Biology

Structural basis and mode of action for two broadly neutralizing antibodies against SARS-CoV-2 emerging variants of concern

Wenwe Li, Yaozong Chen, Jeemie Prevost, Irfan Ullah, Maoli Lu, Shang Yu Gong, Alexandra Tauzin, Romain Gasser, Dani Vezina, Sai Priya Anand, Guillaume Goyette, Debashree Chaterjee, Shilei Ding, William D. Tolbert, Michael W. Grunst, Yuxia Bo, Shijian Zhang, Jonathan Richard, Fei Zhou, Rick K. Huang, Lothar Esser, Allison Zeher, Marceline Cote, Priti Kumar, Joseph Sodroski, Di Xia, Pradeep D. Uchil, Marzena Pazgier, Andres Finzi, Walther Mothes

Summary: This study elucidates the structural basis and mode of action for two potent SARS-CoV-2 spike-neutralizing monoclonal antibodies. CV3-1 triggers shedding of the S1 subunit by binding to a loop structure in the receptor-binding domain (RBD), while CV3-25 inhibits membrane fusion by binding to an epitope in the stem helix region of the S2 subunit. Designing vaccine immunogens that incorporate conserved regions in the RBD and stem helix region could elicit pan-coronavirus protective immune responses.

CELL REPORTS (2022)

Review Immunology

Flagella at the Host-Microbe Interface: Key Functions Intersect With Redundant Responses

Douglas T. Akahoshi, Charles L. Bevins

Summary: Bacteria and other microbes use flagella for locomotion, which brings advantages to the host but also poses threats. The host has developed various immune countermeasures to target and mitigate flagellar threats, including maintaining mucosal structure, molecular recognition, and secretion of effector molecules that inhibit flagellar motility. Studies on flagella are not limited to pathogenic bacteria, but also involve the interaction with flagellated members of the commensal microbiota during homeostasis.

FRONTIERS IN IMMUNOLOGY (2022)

Review Immunology

Virulence Factors of Pseudomonas Aeruginosa and Antivirulence Strategies to Combat Its Drug Resistance

Chongbing Liao, Xin Huang, Qingxia Wang, Dan Yao, Wuyuan Lu

Summary: Pseudomonas aeruginosa is a pathogen that causes nosocomial infections, particularly in severely ill and immunocompromised patients. It is widely distributed in the environment, especially in hospitals, and poses a major threat to human health due to the emergence of drug-resistant strains. The use of antivirulence treatment or combination therapies can effectively reduce virulence without inducing drug resistance.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2022)

Article Immunology

Characterization of an intelectin-1 (Itln1) knockout mouse model

Eric B. Nonnecke, Patricia A. Castillo, Douglas T. Akahoshi, Stephanie M. Goley, Charles L. Bevins, Bo Lonnerdal

Summary: Intelectins are carbohydrate-binding proteins that play a role in innate immunity. They are highly conserved across chordate evolution. Human ITLN1 is abundant in the intestinal mucosa and binds microbial glycans. Mutations in ITLN1 have been linked to susceptibility for diseases like Crohn's disease. Using a mouse model, researchers found that mouse Itln1 is expressed in Paneth cells and may play a minor role in chemically induced colitis or diet-induced obesity.

FRONTIERS IN IMMUNOLOGY (2022)

Article Immunology

Mouse α-Defensins: Structural and Functional Analysis of the 17 Cryptdin Isoforms Identified from a Single Jejunal Crypt

Qingxia Wang, Yilin Yang, Gan Luo, Yang Zhou, William D. Tolbert, Marzena Pazgier, Chongbing Liao, Wuyuan Lu

Summary: The study investigates the bactericidal activities, self-association ability, crystal structure, and molecular dynamics simulation of mouse alpha-defensins, or cryptdins, providing insights into their molecular level function.

INFECTION AND IMMUNITY (2023)

Article Chemistry, Multidisciplinary

Configuration-Specific Antibody for Bacterial Heptosylation: An Antiadhesion Therapeutic Strategy

Xiang Li, Chongbing Liao, Yue Xu, Qiu-He Lu, Si Chen, Li Su, Yan Zou, Feng Shao, Wuyuan Lu, Wei-Dong Zhang, Hong-Gang Hu

Summary: Alternative antibacterial therapies are urgently needed to combat antibiotic resistance. One attractive approach is to inhibit bacterial adhesion and colonization. In this study, researchers synthesized glycopeptides containing a novel glycan structure and generated antibodies that specifically recognize a type of glycosylation found on Gram-negative bacteria, effectively blocking bacterial adhesion and offering new possibilities for the treatment of bacterial infections.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2023)

Article Engineering, Biomedical

Treatment of peanut allergy and colitis in mice via the intestinal release of butyrate from polymeric micelles

Ruyi Wang, Shijie Cao, Mohamed Elfatih H. Bashir, Lauren A. Hesser, Yanlin Su, Sung Min Choi Hong, Andrew Thompson, Elliot Culleen, Matthew Sabados, Nicholas P. Dylla, Evelyn Campbell, Riyue Bao, Eric B. Nonnecke, Charles L. Bevins, D. Scott Wilson, Jeffrey A. Hubbell, Cathryn R. Nagler

Summary: The depletion of beneficial taxa in the gut, including butyrate-producing Clostridia, has led to the increase in food allergies and inflammatory bowel disease. By delivering butyrate-releasing micelles to the intestinal tract, barrier-protective responses can be restored, reducing disease severity in mouse models of colitis and peanut allergy. This approach can potentially treat allergic and inflammatory diseases by restoring microbial and mucosal homeostasis.

NATURE BIOMEDICAL ENGINEERING (2023)

Article Nanoscience & Nanotechnology

Bioactive Spinal Cord Scaffold Releasing Neurotrophic Exosomes to Promote In Situ Centralis Neuroplasticity

Sisi Mi, Zhuo Chang, Xue Wang, Jiaxin Gao, Yu Liu, Wenjia Liu, Wangxiao He, Zhongquan Qi

Summary: Spinal cord injury (SCI) is a severe injury of the central nervous system, causing functional dysfunction and paralysis in millions of patients. A bioactive scaffold, called a spinal cord assembly (SCA), was created using cell-sheet technology and stem cells. This scaffold released neurotrophic exosomes, promoting neuronal regeneration, axonal extension, angiogenesis, and inhibiting glial scar formation in a SCI rat model.

ACS APPLIED MATERIALS & INTERFACES (2023)

Article Microbiology

Flagella-driven motility is a target of human Paneth cell defensin activity

Douglas T. Akahoshi, Dean E. Natwick, Weirong Yuan, Wuyuan Lu, Sean R. Collins, Charles L. Bevins

Summary: Human alpha-defensin 6 (HD6), secreted by Paneth cells of the small intestine, protects against microbes by binding to bacterial surface proteins and self-assembling into fibers and nets, inhibiting flagellar motility. The ability of HD6 to self-assemble is crucial for targeting and restricting bacterial flagellar motility.

PLOS PATHOGENS (2023)

Article Oncology

Estimates of bladder cancer burden attributable to high fasting plasma glucose: Findings of the Global Burden of Disease Study 2019

Ying Wu, Yujiao Deng, Zhijun Dai, Yubo Ma, Lijuan Lyu, Chen Lei, Yi Zheng, Yizhen Li, Ziming Wang, Jie Gao

Summary: Based on the Global Burden of Disease Study 2019, high fasting plasma glucose (FPG) has been identified as a risk factor for bladder cancer globally. The death and DALY rates of bladder cancer attributable to high FPG have significantly increased since 1990, particularly among older males.

CANCER MEDICINE (2023)

Article Engineering, Environmental

Biomimetic peptide dynamic hydrogel inspired by humanized defensin nanonets as the wound-healing gel coating

Juzheng Yuan, Yang Wang, Wenguang Yang, Xiao Li, Kaishan Tao, Wangxiao He, Jin Yan

Summary: In this study, an antimicrobial nanonet with hemostatic function was designed and successfully used to treat chronic wounds associated with multiple bacterial infections. The nanogel not only prevented tissue adhesion but also promoted wound healing. This research provides a promising therapeutic approach for chronic wound therapy and may contribute to the development of biomimetic peptide hydrogels for various human diseases.

CHEMICAL ENGINEERING JOURNAL (2023)

Article Multidisciplinary Sciences

Nitroalkanes as thioacyl equivalents to access thioamides and thiopeptides

Xiaonan Wang, Silong Xu, Yuhai Tang, Martin J. J. Lear, Wangxiao He, Jing Li

Summary: The replacement of oxoamide units with thioamides is an effective strategy to enhance biological activity and resistance to enzymatic degradation in peptide therapeutics. This study presents a direct coupling method using readily available nitroalkanes and amines with elemental sulfur and base to form thioamides and thiopeptides. The developed method allows for selective and stereo-retentive introduction of thioamide bonds into peptide or protein backbones, enabling the synthesis of diverse thioamides in high yields.

NATURE COMMUNICATIONS (2023)

暂无数据