Article
Biochemistry & Molecular Biology
Zuopeng Wu, Rebecca A. Sweet, Gerard F. Hoyne, Charmaine J. Simeonovic, Christopher R. Parish
Summary: It has been accepted for decades that T lymphocytes and metastasising tumour cells traverse basement membranes (BM) by deploying a battery of degradative enzymes, particularly proteases. However, recent studies suggest that there are other mechanisms that allow cell migration through basement membranes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Reese A. Martin, Ann T. Tate
Summary: Genes involved in immune defense resist rapidly evolving parasites and pathogens and are highly represented in the immune system. Pleiotropic signaling genes affect multiple phenotypes and may play a role in the evolution of inducible immunity. Pleiotropy is prevalent in immune signaling networks, and it provides an advantage for host fitness during infection.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xialin Du, Junli Sheng, Yitian Chen, Shitong He, Yalong Yang, Yulan Huang, Yuling Fu, Linmiao Lie, Zhenyu Han, Bo Zhu, Honglin Liu, Qian Wen, Xinying Zhou, Chaoying Zhou, Shengfeng Hu, Li Ma
Summary: The role of ISGylation in the macrophage response to Mycobacterium tuberculosis infection was explored. ISGylation mediated the degradation of PTEN, which promoted the activity of the PI3K-AKT signaling pathway and the synthesis of proinflammatory cytokines, resulting in increased bacterial growth. This finding expands the role of ISGylation in macrophages and suggests HERC5 signaling as a potential target for adjunct host-directed therapy in tuberculosis patients.
Article
Medicine, Research & Experimental
Yongjian Wu, Minhao Wu, Siqi Ming, Xiaoxia Zhan, Shengfeng Hu, Xingyu Li, Huan Yin, Can Cao, Jiao Liu, Jinai Li, Zhilong Wu, Jie Zhou, Lei Liu, Sitang Gong, Duanman He, Xi Huang
Summary: TREM-2 is induced on CD4(+) T cells in response to Mycobacterium tuberculosis infection and plays a critical role in promoting proinflammatory Th1 responses for host defense. The study reveals a potential therapeutic target for infectious and inflammatory diseases by targeting TREM-2.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Bo Yang, Jinyong Pei, Chen Lu, Yi Wang, Mengyang Shen, Xiao Qin, Yulu Huang, Xi Yang, Xin Zhao, Shujun Ma, Zhishan Song, Yinming Liang, Hui Wang, Jie Wang
Summary: This study reveals that RNF144A interacts with STING and enhances its translocation from the ER to the Golgi through K6-linked ubiquitination, thereby promoting the signaling pathways triggered by DNA virus or cytosolic DNA. RNF144A overexpression enhances immune responses, while knockdown of RNF144A has the opposite effect.
Article
Biochemistry & Molecular Biology
Yuling Fu, Peng Wang, Jingjing Zhao, Yunke Tan, Junli Sheng, Shitong He, Xialin Du, Yulan Huang, Yalong Yang, Jinling Li, Yuxiong Cai, Yuxuan Liu, Shengfeng Hu
Summary: USP12 is identified as a critical regulator of CD4(+) T cell activation, promoting the phenotype and signaling of these cells. While USP12-deficient CD4(+) T cells protect mice from autoimmune diseases, they attenuate immune responses against bacterial infections.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Virology
Qingxia Gao, Meijun Jiang, Yaxin Zhao, Guoli Li, Cha Yang, Caiyue Ren, Meilin Jin, Huanchun Chen, Hongbo Zhou
Summary: This study identifies eIF4A3 as a negative regulator of virus-induced type I interferon production by impairing the activation of IRF3. This finding sheds light on the mechanism by which eIF4A3 promotes replication of RNA viruses and provides insights into potential therapeutic strategies for viral infectious diseases.
JOURNAL OF VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Ming Kuang, Yingchi Zhao, Haitao Yu, Siji Li, Tianyi Liu, Luoying Chen, Jingxuan Chen, Yujie Luo, Xuefei Guo, Xuemei Wei, Yunfei Li, Zeming Zhang, Dandan Wang, Fuping You
Summary: XAF1 acts as an epigenetic regulator that promotes the opening of chromatin and activation of antiviral immunity by targeting TRIM28 during infection. It de-SUMOylates TRIM28, leading to increased accessibility of the chromatin and robust induction of antiviral genes. XAF1 deficiency renders mice susceptible to RNA viruses due to impaired induction of antiviral genes.
Article
Immunology
Na Zhang, Fei Wang, Gaomeng Zhang, Qi Zhang, Yuhong Liu, Qiao Wang, Mohamed Shafey Elsharkawy, Maiqing Zheng, Jie Wen, Guiping Zhao, Qinghe Li
Summary: Toll-like receptors (TLRs) are important immune sensors involved in host defense. In this study, the researchers discovered that the deubiquitinase USP7 interacts with MyD88 protein, regulating its expression and participating in bacteria-induced inflammation. This finding contributes to our understanding of the regulatory mechanisms in immune signaling.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Rathi Saravanan, Yeu Khai Choong, Chun Hwee Lim, Li Ming Lim, Jitka Petrlova, Artur Schmidtchen
Summary: Cell-free DNA (cfDNA) is a major component of neutrophil extracellular traps (NETs), which play a critical role in innate immune response to infection. Recent studies have shown that NETs have procoagulant activity and can trigger thrombin generation through the intrinsic pathway of coagulation. In vitro experiments have shown that DNA binding can lead to thrombin autolysis and generation of thrombin-derived C-terminal peptides (TCPs), which can bind to NETs and provide protection against degradation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiaoyan Wang, Jing Xiong, Diwei Zhou, Shanfeng Zhang, Li Wang, Qingqing Tian, Changming Li, Jie Liu, Yaping Wu, Junying Li, Jun Wang
Summary: This study uncovered the role of TRIM34 in regulating IAV-induced programmed cell death by mediating the K63-linked polyubiquitination of ZBP1. The interaction between TRIM34 and ZBP1 protected mice from inflammatory responses and epithelial damage during IAV infection. Higher levels of ZBP1 were found to correlate with increased proinflammatory cytokines in IAV-infected patients.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biology
Jee Yoon Bang, Julia Kathryn Sunstrum, Danielle Garand, Gustavo Morrone Parfitt, Melanie Woodin, Wataru Inoue, Junchul Kim
Summary: This study reveals a new mechanism for experience-dependent, top-down control of innate defensive behaviors in animals, showing that the anterior hypothalamic nucleus is the key brain region involved, with the hippocampus transmitting information through this pathway to control memory and escape behaviors in prey.
Article
Multidisciplinary Sciences
Pablo S. Contreras, Pablo J. Tapia, Eutteum Jeong, Sourish Ghosh, Nihal Altan-Bonnet, Rosa Puertollano
Summary: Beta-coronaviruses pose a severe threat to global health. Understanding the interaction between host and beta-coronaviruses is crucial for comprehending disease pathogenesis and developing effective treatments. This study reveals that TFEB and TFE3, transcription factors, translocate into the nucleus upon beta-coronavirus infection through the activation of calcineurin phosphatase. In the nucleus, TFEB and TFE3 bind to the promoters of lysosomal and immune genes, influencing the immune response and viral infectivity.
Article
Multidisciplinary Sciences
Jona Karam, Fabien P. Blanchet, Eric Vives, Prisca Boisguerin, Yves-Marie Boudehen, Laurent Kremer, Wassim Daher
Summary: It has been discovered that neutralizing anti-CD81 antibodies and deletion of the large extracellular loop (LEL) of CD81 significantly reduce the uptake of Mab by macrophages. Saturation of Mab with soluble GST-CD81-LEL or CD81-LEL-derived peptides also decreases the internalization of the bacteria. The study unveils AhpC as a major interactant of CD81-LEL, and pre-exposure of macrophages with soluble AhpC inhibits mycobacterial uptake while overexpression of AhpC in Mab enhances its internalization. These findings highlight the previously unexplored role of CD81/AhpC in promoting the uptake of pathogenic mycobacteria by host cells.
Article
Immunology
Melanie D. Balhuizen, Chantal M. Versluis, Monica O. van Grondelle, Edwin J. A. Veldhuizen, Henk P. Haagsman
Summary: Antibiotic resistance is increasing, and bacterial vaccines, such as outer membrane vesicles (OMVs) produced by Gram-negative bacteria, can be used to prevent resistance development. Host defense peptides (HDPs), specifically cathelicidins, have been found to modulate immune responses by interacting with OMVs and neutralizing LPS-induced TLR4 activation. Additionally, TLR2, 4, 5, and 9 play a role in macrophage stimulation by OMVs.
Article
Multidisciplinary Sciences
Pradeep Chopra, Apoorva Joshi, Jiandong Wu, Weigang Lu, Tejabhiram Yadavalli, Margreet A. Wolfert, Deepak Shukla, Joseph Zaia, Geert-Jan Boons
Summary: This study introduced a modular synthetic approach to create diverse HS oligosaccharides with or without 3-OS. These oligosaccharides were used to examine ligand requirements for HS-binding proteins on a glycan microarray. The study also found that 3-OS influenced cleavage by lyase II while 2-OS only affected digestion by lyase I, showing varied substrate specificities among heparin lyases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Benjamin A. Turturice, Juliana Theorell, Mary Dawn Koenig, Lisa Tussing-Humphreys, Diane R. Gold, Augusto A. Litonjua, Emily Oken, Sheryl L. Rifas-Shiman, David L. Perkins, Patricia W. Finn
Summary: This study identified specific perinatal characteristics associated with pediatric asthma risk and identified transcriptional changes as mediators of this risk. The abundance of neutrophil-specific granules at birth was found to predict risk for pediatric asthma and pulmonary function in adolescence.
Article
Virology
Ghadah A. Karasneh, Divya Kapoor, Navya Bellamkonda, Chandrashekhar D. Patil, Deepak Shukla
Summary: The increased levels of HPSE can reduce syncytial plaque formation and promote viral egress and release. Transiently enhanced expression of HPSE does not affect HSV-1 entry into cells but facilitates extracellular release of mature virions.
Article
Multidisciplinary Sciences
Joshua Ames, Tejabhiram Yadavalli, Rahul Suryawanshi, James Hopkins, Alexander Agelidis, Chandrashekhar Patil, Brian Fredericks, Henry Tseng, Tibor Valyi-Nagy, Deepak Shukla
Summary: The study demonstrates that the autophagy receptor OPTN plays a crucial neuroprotective role during HSV-1 infection by degrading viral proteins, preventing virus spread and neuronal necroptosis. Lack of OPTN leads to cognitive decline and susceptibility to lethal CNS infection in mice, indicating its importance in survival from potentially deadly viral infections.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Rahul K. Suryawanshi, Chandrashekhar D. Patil, Raghuram Koganti, Sudhanshu Kumar Singh, Joshua M. Ames, Deepak Shukla
Summary: Research indicates that cationic peptides G1 and G2 may inhibit the entry of SARS-CoV-2 by reducing the essential receptor HS on cell surfaces and interfering with the virus interaction with ACE2.
Editorial Material
Cell Biology
Chandrashekhar D. Patil, Deepak Shukla
Summary: Very little is known about the mechanisms that restrict neurotropic herpesviruses from infecting the central nervous system and causing neuron death. However, recent research has shown that OPTN-mediated autophagy acts as an intrinsic immune barrier against these viruses and protects the CNS from neurodegenerative stress.
Article
Immunology
Chandrashekhar D. Patil, Rahul Suryawanshi, Joshua Ames, Raghuram Koganti, Alex Agelidis, Divya Kapoor, Tejabhiram Yadavalli, Lulia Koujah, Henry C. Tseng, Deepak Shukla
Summary: This study reveals the key role of optineurin (OPTN) in restricting HSV-2 infection and controlling viral spread. Lack of OPTN leads to enhanced virus production and impaired host autophagy response. The OPTN/CCL5 nexus identified in this study may represent an intrinsic host defense mechanism against herpesviruses.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Virology
Ilina Bhattacharya, Tejabhiram Yadavalli, David Wu, Deepak Shukla
Summary: This study demonstrates the antiviral activity of plasma membrane-derived liposomes, especially in preventing HSV-1 infection. The research shows that cellular liposomes expressing viral entry-specific cell surface protein receptors exhibit robust antiviral activity, while those lacking the relevant HSV-1 entry receptors do not.
Article
Virology
Tejabhiram Yadavalli, Pankaj Sharma, David Wu, Divya Kapoor, Deepak Shukla
Summary: CREB3 plays a key role in HPSE-facilitated HSV-1 egress. HPSE expression is correlated with CREB3 expression, and HPSE-transfected cells show higher CREB3 expression, while HPSE knockout cells show lower CREB3 expression. CREB3-transfected cells exhibit significantly increased export of HPSE upon infection. Additionally, COPII, which mediates HPSE trafficking, is upregulated via a CREB3-dependent pathway during HSV-1 infection. Co-transfection of CREB3 and HPSE results in the highest viral release.
Article
Multidisciplinary Sciences
Nicholas W. Hubbard, Joshua M. Ames, Megan Maurano, Lan H. Chu, Kim Y. Somfleth, Nandan S. Gokhale, Margo Werner, Jessica M. Snyder, Katrina Lichauco, Ram Savan, Daniel B. Stetson, Andrew Oberst
Summary: The RNA-editing enzyme ADAR1 inhibits innate immune activation and pathology by disrupting the duplex structure of endogenous double-stranded RNA species. Alteration of the Z-DNA-binding domain (ZBD) of ADAR1 leads to activation of ZBP1, causing autoinflammatory pathology.
Article
Multidisciplinary Sciences
Rahul K. Suryawanshi, Chandrashekhar D. Patil, Alex Agelidis, Raghuram Koganti, Tejabhiram Yadavalli, Joshua M. Ames, Hemant Borase, Deepak Shukla
Summary: This study found that compared to animals lacking HPSE, wild-type mice exhibit notable pathophysiology during HSV-1 reinfection. HPSE promotes infected cell survival and supports the formation of a pro-disease environment. In contrast, lack of HPSE enhances intrinsic immunity by promoting cytokine expression, inducing necroptosis of infected cells, and decreasing leukocyte infiltration into the cornea. Overall, recent prior infection immunity fails to abolish disease manifestation during HSV-1 reinfection unless HPSE is rendered inactive.
Article
Medicine, Research & Experimental
Tejabhiram Yadavalli, Sudhanshu Kumar Singh, Abhijit A. Date, Deepak Shukla
Summary: This study evaluated the acute and short-term toxicity of orally administered BX795 in mice, as well as its pharmacokinetics and tissue distribution. The results showed that orally administered BX795 was well tolerated, had an oral bioavailability of 56%, and reached ocular and genital tissues within the first 15 min of dosing. The study indicated that orally administered BX795 can significantly reduce herpesvirus replication in ocular and genital tissue.
BIOMEDICINE & PHARMACOTHERAPY
(2023)