DOCSLIB.ORG

NOD-Like Receptors in Lung Diseases

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
NOD-Like Receptors in Lung Diseases REVIEW ARTICLE published: 21 November 2013 doi: 10.3389/fimmu.2013.00393 NOD-like receptors in lung diseases Catherine Chaput, Leif Erik Sander, Norbert Suttorp and Bastian Opitz* Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany Edited by: The lung is a particularly vulnerable organ at the interface of the body and the exterior Thomas A. Kufer, University of environment. It is constantly exposed to microbes and particles by inhalation. The innate Cologne, Germany immune system needs to react promptly and adequately to potential dangers posed by Reviewed by: Dario S. Zamboni, Universidade de these microbes and particles, while at the same time avoiding extensive tissue damage. São Paulo, Brazil Nucleotide-binding oligomerization domain-like receptors (NLRs) represent a group of key Jose A. Bengoechea, Queen’s sensors for microbes and damage in the lung. As such they are important players in various University Belfast, UK infectious as well as acute and chronic sterile inflammatory diseases, such as pneumonia, *Correspondence: chronic obstructive pulmonary disease (COPD), acute lung injury/acute respiratory distress Bastian Opitz, Department of Internal Medicine/Infectious Diseases and syndrome, pneumoconiosis, and asthma. Activation of most known NLRs leads to the pro- Pulmonary Medicine, duction and release of pro-inflammatory cytokines, and/or to the induction of cell death. Charité – Universitätsmedizin Berlin, We will review NLR functions in the lung during infection and sterile inflammation. Augustenburger Platz 1, 13353 Berlin, Germany Keywords: NOD-like receptors, inflammasome, lung, pneumonia, lung injury e-mail: [email protected] INTRODUCTION cell and tissue integrity by so-called pattern-recognition recep- The respiratory tract constitutes a large surface of the body with the tors (PRRs). PRRs comprise different protein families such as the outside environment that is exposed to high volume airflow and transmembrane Toll-like receptors (TLRs) and the intracellularly large numbers of inhaled microbes and particles. The microflora of located nucleotide-binding oligomerization domain (NOD)-like the upper respiratory tract consists of non-pathogenic bacteria but receptors (NLRs) (10–12). PRRs recognize conserved microbial also frequently comprises potential pathogens such as Streptococ- molecules, referred to as pathogen-associated molecular patterns cus pneumoniae and Staphylococcus aureus (1). The distal bronchi (PAMPs) (13). However, recent evidence suggests that recogni- and the alveoli have long been considered sterile, however more tion of disturbed host cell integrity and danger signals might recently microbes that are either aspirated from the upper respira- also play a role in the immune responses to invading pathogens tory tract (2) or constantly reside in the lower airways (3, 4) have (see below). In contrast to the original paradigm (13) it is now been found by culture-independent approaches. well-accepted that PRRs also sense non-microbial ligands gener- Inflammatory disorders of the respiratory tract involving the ated during sterile tissue damage, often called damage-associated innate immune system include both infectious and non-infectious molecular patterns (DAMPs) (14, 15). Moreover, some PRRs can diseases. Lower respiratory tract infections, or pneumonia, gener- additionally respond to large particles and therefore appear to be ally develop when facultative pathogenic microbes that colonize key mediators in pneumoconiosis (16–18). the upper respiratory tract are aspirated or airborne pathogens The NLR family comprises 22 members in humans and even are inhaled. The World Health Organization (WHO) estimates more in mice. Most NLRs share common structural character- 429 million cases of acute lower respiratory tract infections in istics including a C-terminal leucine-rich repeat (LRR) domain, 2004, making it the third leading cause of death world-wide (5). often involved in ligand recognition, a central NOD, and a vari- Moreover, non-infectious and chronic lung diseases substantially able N-terminal effector domain (10). Based on the type of effector contribute to morbidity. Chronic obstructive pulmonary disease domains that is either a caspase recruitment domain (CARD), a (COPD) is mainly caused by tobacco smoke and can exacerbate pyrin domain (PYD), or a baculoviral inhibitor of apoptosis pro- during acute infections, ranks as the number four leading cause of tein repeat (BIR) domain, the NLR family can be further divides death in most industrialized countries (5). Acute lung injury (ALI) into five subfamilies. The NLRA subfamily consist of only one and its severest form, called acute respiratory distress syndrome member, the transcription factor CIITA, of which at least one (ARDS), can develop after infectious as well as non-infectious splice variant expresses a CARD (Figure 1). CIITA is involved insults (6). Another potentially life-threatening disorder is allergic in transcriptional activation of genes encoding major histocom- asthma, which is characterized by airway hyperresponsiveness due patibility complex class II [for detailed discussion of this unique to allergen-triggered airway inflammation causing chronic recur- NLR protein we refer to Ref. (19)]. The NLRB group of NLRs rent airflow obstruction. Long-term exposure to silica, asbestos, or expresses a BIR domain and consists of NAIP1–7 in mice and NAIP coal particles can cause chronic occupational lung disease called in humans. The NLRC subfamily includes the CARD-containing pneumoconiosis. molecules NOD1, NOD2, and NLRC3–5, whereas the 14 known The innate immune system is a key player in various infectious NLRP proteins (NLRP1–14) express a PYD. NLRX1 is the only and non-infectious disorders of the lung (7–9). It senses infec- member of the NLRX subgroup, and the only NLR protein that is tions, sterile tissue damage, and probably any disturbance of host localized in mitochondria (10, 20). Whereas some NLR proteins www.frontiersin.org November 2013 | Volume 4 | Article 393 | 1 Chaput et al. NOD-like receptors in lung diseases FIGURE 1 | Summary of the main characteristics of the NLRs. h and m symbolized a characteristic specific to human or mouse. For more details, refer to the main text. function as bona fide PRRs, other family members act as adaptor predominantly in Gram-negative bacteria (33, 34). NOD2 rec- molecules or regulators of signal transduction. ognizes the muramyl-dipeptide (MDP) MurNAc-l-Ala-d-isoGln, In this review article we discuss the current knowledge about which is conserved in peptidoglycans of the majority of bacteria NLR expression and function in the lung in different pulmonary (35, 36). Other peptidoglycan motifs can be recognized by NOD1 diseases. We have grouped the NLRs based on functional similar- and NOD2, for details refer to review (37). ities and summarize major pathways and common principles of Ligand recognition by both receptors leads to signal transduc- function. tion through Rip2 kinase with downstream activation of MAP kinases and the transcription factor NF-kB, leading to activation NOD1 AND NOD2 of genes encoding different cytokines, chemokines (e.g., IL-8), NOD1 and NOD2 were the first NLR proteins to be discovered and antimicrobial peptides. Both NOD signaling cascades are (21–25). In the lung, NOD1 is expressed in various cell types regulated by small GTPases such as Rac1, however conflicting evi- including lung epithelial cells, endothelial cells, human airway dence exists as to whether this regulation enhances or reduces smooth muscle cells, and different types of leukocytes (26–29). NOD-dependent NF-kB activation (38–40). A recent study sug- NOD2 has been found in alveolar macrophages, neutrophils, and gested that Rac1 is activated upstream of NOD1, and that NOD1 bronchial epithelial cells (30–32). NOD1 responds to bacterial cell essentially senses GTPase activation rather than the peptidoglycan wall peptidoglycan containing meso-diaminopimelic acid found fragments directly (41). NOD1 and NOD2 can recruit the GTPase Frontiers in Immunology | Molecular Innate Immunity November 2013 | Volume 4 | Article 393| 2 Chaput et al. NOD-like receptors in lung diseases ATG16L1 and subsequently stimulate autophagy, a highly con- NOD2-activating potential compared to the MDP (53). NOD2 served bulk degradation system with antimicrobial activity against controls inflammatory responses to S. aureus pneumonia (49), intracellular pathogens (42). and it is also required to clear pneumococcal colonization of the Among the studied lung pathogens, NOD1 responds to upper respiratory tract by CCR2-dependently recruited mono- Chlamydophila pneumoniae, Legionella pneumophila, Klebsiella cytes/macrophages. It was shown that professional phagocytes pneumoniae, Haemophilus influenzae, and Pseudomonas aerug- produce CCL2 after LysM-mediated bacterial digestion and subse- inosa (32, 40, 43–47), whereas NOD2 senses S. pneumoniae, quent NOD2-dependent detection of S. pneumoniae-derived pep- S. aureus, Escherichia coli, C. pneumoniae, and Mycobacterium tidoglycan (48). Similarly, NOD1 controls neutrophil-dependent −/− tuberculosis (30–32, 44, 48–50)(Figure 2). Accordingly, Rip2 clearance of nasopharyngeal colonization with encapsulated H. −/− −/− mice – and to a lesser extend also Nod1 and Nod2 mice – influenzae in mice, whereas it is redundant for non-encapsulated display impaired chemokine production, neutrophil recruitment, strains (46). NOD1 might critically
Load more

Recommended publications
  • The Role of Vimentin and the NLRP3 Inflammasome in Influenza a Infection
    The Role of Vimentin and the NLRP3 Inflammasome in Influenza A Infection A Senior Thesis Presented to The Faculty of the Department of Molecular Biology, Colorado College By Maggie Turner Bachelor of Arts Degree in Molecular Biology April 28, 2017 ________________________ Dr. Olivia Hatton Primary Thesis Advisor __________________________ Dr. Sara Hanson Secondary Thesis Advisor ABSTRACT Infection with Influenza A virus (IAV) continues to cause morbidity and mortality in children across the globe, in part due to the excessive inflammatory response during pathogen clearance. Using a murine model of IAV infection, this study focuses on the role of the innate immune system in IAV infection through the scope of NLRP3 inflammasome protein activation and assembly. We were able to detect the presence of the NLRP3-inflammasome target proteins ASC, Pro-caspase-1, NLRP3, RIG-1, and IL- 1β in both juvenile and adult mice. Notably, we found significantly increased levels of ASC and RIG-1 protein in juveniles compared to adults. This suggests that ASC and RIG-1 are related to the observed excessive inflammatory response upon IAV infection in juveniles. To examine NLRP3-inflammasome assembly, we created multiple mutant constructs of the inflammasome scaffolding protein Vimentin as well as vimentin-/- cells. IL-1β production was greatly inhibited in vimentin-/- cells compared to the wild type upon activation of the NLRP3 inflammasome. The same trend was seen when only the head region of the protein was present. We suggest that the intermediate filament (IF) Vimentin serves as a protein scaffold for inflammasome assembly, and that expression of Vimentin is a necessary checkpoint in the innate immune response.
    [Show full text]
  • Bayesian Hierarchical Modeling of High-Throughput Genomic Data with Applications to Cancer Bioinformatics and Stem Cell Differentiation
    BAYESIAN HIERARCHICAL MODELING OF HIGH-THROUGHPUT GENOMIC DATA WITH APPLICATIONS TO CANCER BIOINFORMATICS AND STEM CELL DIFFERENTIATION by Keegan D. Korthauer A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Statistics) at the UNIVERSITY OF WISCONSIN–MADISON 2015 Date of final oral examination: 05/04/15 The dissertation is approved by the following members of the Final Oral Committee: Christina Kendziorski, Professor, Biostatistics and Medical Informatics Michael A. Newton, Professor, Statistics Sunduz Kele¸s,Professor, Biostatistics and Medical Informatics Sijian Wang, Associate Professor, Biostatistics and Medical Informatics Michael N. Gould, Professor, Oncology © Copyright by Keegan D. Korthauer 2015 All Rights Reserved i in memory of my grandparents Ma and Pa FL Grandma and John ii ACKNOWLEDGMENTS First and foremost, I am deeply grateful to my thesis advisor Christina Kendziorski for her invaluable advice, enthusiastic support, and unending patience throughout my time at UW-Madison. She has provided sound wisdom on everything from methodological principles to the intricacies of academic research. I especially appreciate that she has always encouraged me to eke out my own path and I attribute a great deal of credit to her for the successes I have achieved thus far. I also owe special thanks to my committee member Professor Michael Newton, who guided me through one of my first collaborative research experiences and has continued to provide key advice on my thesis research. I am also indebted to the other members of my thesis committee, Professor Sunduz Kele¸s,Professor Sijian Wang, and Professor Michael Gould, whose valuable comments, questions, and suggestions have greatly improved this dissertation.
    [Show full text]
  • NOD-Like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy
    International Journal of Molecular Sciences Review NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy Rayne R. Lim 1,2,3, Margaret E. Wieser 1, Rama R. Ganga 4, Veluchamy A. Barathi 5, Rajamani Lakshminarayanan 5 , Rajiv R. Mohan 1,2,3,6, Dean P. Hainsworth 6 and Shyam S. Chaurasia 1,2,3,* 1 Ocular Immunology and Angiogenesis Lab, University of Missouri, Columbia, MO 652011, USA; [email protected] (R.R.L.); [email protected] (M.E.W.); [email protected] (R.R.M.) 2 Department of Biomedical Sciences, University of Missouri, Columbia, MO 652011, USA 3 Ophthalmology, Harry S. Truman Memorial Veterans’ Hospital, Columbia, MO 652011, USA 4 Surgery, University of Missouri, Columbia, MO 652011, USA; [email protected] 5 Singapore Eye Research Institute, Singapore 169856, Singapore; [email protected] (V.A.B.); [email protected] (R.L.) 6 Mason Eye Institute, School of Medicine, University of Missouri, Columbia, MO 652011, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-573-882-3207 Received: 9 December 2019; Accepted: 27 January 2020; Published: 30 January 2020 Abstract: Diabetic retinopathy (DR) is an ocular complication of diabetes mellitus (DM). International Diabetic Federations (IDF) estimates up to 629 million people with DM by the year 2045 worldwide. Nearly 50% of DM patients will show evidence of diabetic-related eye problems. Therapeutic interventions for DR are limited and mostly involve surgical intervention at the late-stages of the disease. The lack of early-stage diagnostic tools and therapies, especially in DR, demands a better understanding of the biological processes involved in the etiology of disease progression.
    [Show full text]
  • Post-Translational Regulation of Inflammasomes
    OPEN Cellular & Molecular Immunology (2017) 14, 65–79 & 2017 CSI and USTC All rights reserved 2042-0226/17 www.nature.com/cmi REVIEW Post-translational regulation of inflammasomes Jie Yang1,2, Zhonghua Liu1 and Tsan Sam Xiao1 Inflammasomes play essential roles in immune protection against microbial infections. However, excessive inflammation is implicated in various human diseases, including autoinflammatory syndromes, diabetes, multiple sclerosis, cardiovascular disorders and neurodegenerative diseases. Therefore, precise regulation of inflammasome activities is critical for adequate immune protection while limiting collateral tissue damage. In this review, we focus on the emerging roles of post-translational modifications (PTMs) that regulate activation of the NLRP3, NLRP1, NLRC4, AIM2 and IFI16 inflammasomes. We anticipate that these types of PTMs will be identified in other types of and less well-characterized inflammasomes. Because these highly diverse and versatile PTMs shape distinct inflammatory responses in response to infections and tissue damage, targeting the enzymes involved in these PTMs will undoubtedly offer opportunities for precise modulation of inflammasome activities under various pathophysiological conditions. Cellular & Molecular Immunology (2017) 14, 65–79; doi:10.1038/cmi.2016.29; published online 27 June 2016 Keywords: inflammasome; phosphorylation; post-translational modifications; ubiquitination INTRODUCTION upstream sensor molecules through its PYD domain and The innate immune system relies on pattern recognition downstream
    [Show full text]
  • ATP-Binding and Hydrolysis in Inflammasome Activation
    molecules Review ATP-Binding and Hydrolysis in Inflammasome Activation Christina F. Sandall, Bjoern K. Ziehr and Justin A. MacDonald * Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada; [email protected] (C.F.S.); [email protected] (B.K.Z.) * Correspondence: [email protected]; Tel.: +1-403-210-8433 Academic Editor: Massimo Bertinaria Received: 15 September 2020; Accepted: 3 October 2020; Published: 7 October 2020 Abstract: The prototypical model for NOD-like receptor (NLR) inflammasome assembly includes nucleotide-dependent activation of the NLR downstream of pathogen- or danger-associated molecular pattern (PAMP or DAMP) recognition, followed by nucleation of hetero-oligomeric platforms that lie upstream of inflammatory responses associated with innate immunity. As members of the STAND ATPases, the NLRs are generally thought to share a similar model of ATP-dependent activation and effect. However, recent observations have challenged this paradigm to reveal novel and complex biochemical processes to discern NLRs from other STAND proteins. In this review, we highlight past findings that identify the regulatory importance of conserved ATP-binding and hydrolysis motifs within the nucleotide-binding NACHT domain of NLRs and explore recent breakthroughs that generate connections between NLR protein structure and function. Indeed, newly deposited NLR structures for NLRC4 and NLRP3 have provided unique perspectives on the ATP-dependency of inflammasome activation. Novel molecular dynamic simulations of NLRP3 examined the active site of ADP- and ATP-bound models. The findings support distinctions in nucleotide-binding domain topology with occupancy of ATP or ADP that are in turn disseminated on to the global protein structure.
    [Show full text]
  • Inflammasome Activation and Regulation
    Zheng et al. Cell Discovery (2020) 6:36 Cell Discovery https://doi.org/10.1038/s41421-020-0167-x www.nature.com/celldisc REVIEW ARTICLE Open Access Inflammasome activation and regulation: toward a better understanding of complex mechanisms Danping Zheng1,2,TimurLiwinski1,3 and Eran Elinav 1,4 Abstract Inflammasomes are cytoplasmic multiprotein complexes comprising a sensor protein, inflammatory caspases, and in some but not all cases an adapter protein connecting the two. They can be activated by a repertoire of endogenous and exogenous stimuli, leading to enzymatic activation of canonical caspase-1, noncanonical caspase-11 (or the equivalent caspase-4 and caspase-5 in humans) or caspase-8, resulting in secretion of IL-1β and IL-18, as well as apoptotic and pyroptotic cell death. Appropriate inflammasome activation is vital for the host to cope with foreign pathogens or tissue damage, while aberrant inflammasome activation can cause uncontrolled tissue responses that may contribute to various diseases, including autoinflammatory disorders, cardiometabolic diseases, cancer and neurodegenerative diseases. Therefore, it is imperative to maintain a fine balance between inflammasome activation and inhibition, which requires a fine-tuned regulation of inflammasome assembly and effector function. Recently, a growing body of studies have been focusing on delineating the structural and molecular mechanisms underlying the regulation of inflammasome signaling. In the present review, we summarize the most recent advances and remaining challenges in understanding the ordered inflammasome assembly and activation upon sensing of diverse stimuli, as well as the tight regulations of these processes. Furthermore, we review recent progress and challenges in translating inflammasome research into therapeutic tools, aimed at modifying inflammasome-regulated human diseases.
    [Show full text]
  • AIM2 and NLRC4 Inflammasomes Contribute with ASC to Acute Brain Injury Independently of NLRP3
    AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3 Adam Denesa,b,1, Graham Couttsb, Nikolett Lénárta, Sheena M. Cruickshankb, Pablo Pelegrinb,c, Joanne Skinnerb, Nancy Rothwellb, Stuart M. Allanb, and David Broughb,1 aLaboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, Budapest, 1083, Hungary; bFaculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom; and cInflammation and Experimental Surgery Unit, CIBERehd (Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas), Murcia Biohealth Research Institute–Arrixaca, University Hospital Virgen de la Arrixaca, 30120 Murcia, Spain Edited by Vishva M. Dixit, Genentech, San Francisco, CA, and approved February 19, 2015 (received for review November 18, 2014) Inflammation that contributes to acute cerebrovascular disease is or DAMPs, it recruits ASC, which in turn recruits caspase-1, driven by the proinflammatory cytokine interleukin-1 and is known causing its activation. Caspase-1 then processes pro–IL-1β to a to exacerbate resulting injury. The activity of interleukin-1 is regu- mature form that is rapidly secreted from the cell (5). The ac- lated by multimolecular protein complexes called inflammasomes. tivation of caspase-1 can also cause cell death (6). There are multiple potential inflammasomes activated in diverse A number of inflammasome-forming PRRs have been iden- diseases, yet the nature of the inflammasomes involved in brain tified, including NLR family, pyrin domain containing 1 (NLRP1); injury is currently unknown. Here, using a rodent model of stroke, NLRP3; NLRP6; NLRP7; NLRP12; NLR family, CARD domain we show that the NLRC4 (NLR family, CARD domain containing 4) containing 4 (NLRC4); AIM 2 (absent in melanoma 2); IFI16; and AIM2 (absent in melanoma 2) inflammasomes contribute to and RIG-I (5).
    [Show full text]
  • Dysregulation of Escherichia Coli Α-Hemolysin Expression Alters The
    Dysregulation of Escherichia coli α-hemolysin PNAS PLUS expression alters the course of acute and persistent urinary tract infection Kanna Nagamatsua, Thomas J. Hannanb, Randi L. Guestc, Maria Kostakiotia,1, Maria Hadjifrangiskoua,d, Jana Binkleya, Karen Dodsona, Tracy L. Raivioc, and Scott J. Hultgrena,e,2 Departments of aMolecular Microbiology and Microbial Pathogenesis and bPathology and Immunology, eCenter for Women’s Infections Disease Research, Washington University School of Medicine, St. Louis, MO 63110; cDepartment of Biological Sciences, University of Alberta, Edmonton, AB, Canada T6G 2E9; and dDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232 Contributed by Scott J. Hultgren, January 14, 2015 (sent for review September 10, 2014) Urinary tract infections (UTIs) are among the most common bacterial previously shown to be dependent upon the function of Caspases infections, causing considerable morbidity in females. Infection is (4), the specific host and bacterial factors that modulate bladder highly recurrent despite appropriate antibiotic treatment. Uropa- cell death and exfoliation during the course of a UTI remain thogenic Escherichia coli (UPEC), the most common causative agent poorly understood. of UTIs, invades bladder epithelial cells (BECs) and develops into Approximately 40–50% of E. coli isolated from patients with clonal intracellular bacterial communities (IBCs). Upon maturation, a UTI encodes a secreted pore-forming toxin known as α-hemolysin IBCs disperse, with bacteria spreading to neighboring BECs to repeat (HlyA) (9). Expression of HlyA in UPEC has been previously im- this cycle. This process allows UPEC to gain a foothold in the face of plicated in urothelial cell toxicity in vitro (10, 11) and increased innate defense mechanisms, including micturition, epithelial exfoli- urothelial damage in vivo (12).
    [Show full text]
  • Complementary Regulation of Caspase-1 and IL-1Β Reveals Additional Mechanisms of Dampened Inflammation in Bats
    Complementary regulation of caspase-1 and IL-1β reveals additional mechanisms of dampened inflammation in bats Geraldine Goha,1, Matae Ahna,1, Feng Zhua, Lim Beng Leea, Dahai Luob,c, Aaron T. Irvinga,d,2, and Lin-Fa Wanga,e,2 aProgramme in Emerging Infectious Diseases, Duke–National University of Singapore Medical School, 169857, Singapore; bLee Kong Chian School of Medicine, Nanyang Technological University, 636921, Singapore; cNTU Institute of Structural Biology, Nanyang Technological University, 636921, Singapore; dZhejiang University–University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University International Campus, Haining, 314400, China; and eSinghealth Duke–NUS Global Health Institute, 169857, Singapore Edited by Vishva M. Dixit, Genentech, San Francisco, CA, and approved September 14, 2020 (received for review February 21, 2020) Bats have emerged as unique mammalian vectors harboring a experimental confirmation is rare. We recently demonstrated diverse range of highly lethal zoonotic viruses with minimal that NLRP3 is dampened in bats as a result of loss-of-function clinical disease. Despite having sustained complete genomic loss bat-specific isoforms and impaired transcriptional priming (9). of AIM2, regulation of the downstream inflammasome response in The stimulator of IFN genes (STING), a key adaptor to the bats is unknown. AIM2 sensing of cytoplasmic DNA triggers ASC DNA-sensing cGAS protein, is also exclusively mutated at S358 aggregation and recruits caspase-1, the central inflammasome ef- in bats, resulting in a reduced IFN response to HSV1 (10). We fector enzyme, triggering cleavage of cytokines such as IL-1β and previously reported a complete absence of Absent in melanoma inducing GSDMD-mediated pyroptotic cell death.
    [Show full text]
  • Product Information Sheet for NR-20721
    Product Information Sheet for NR-20721 Monoclonal Anti-Human NLRP4 (NALP4), be stored at -20°C or colder immediately upon arrival. Freeze-thaw cycles should be avoided. Clone U54.M.hNALP4.8 (produced in vitro) Functional Activity: Catalog No. NR-20721 NR-20721 reacts with human NLRP4 in ELISA and western blot assays. See Certificate of Analysis for details. The For research use only. Not for human use. antibody is also reported to function in immunoprecipitation.1 Contributor: Citation: Richard J. Ulevitch, Ph.D., and Luc Teyton, M.D., Ph.D., Acknowledgment for publications should read “The following Department of Immunology and Microbial Science, The reagent was obtained through BEI Resources, NIAID, NIH: Scripps Research Institute, La Jolla, CA, USA` Monoclonal Anti-Human NLRP4 (NALP4), Clone U54.M.hNALP4.8 (produced in vitro), NR-20721.” Manufacturer: BEI Resources Biosafety Level: 1 Appropriate safety procedures should always be used with Product Description: this material. Laboratory safety is discussed in the following Antibody Class: IgG1κ publication: U.S. Department of Health and Human Services, Mouse monoclonal antibody prepared against the human Public Health Service, Centers for Disease Control and NLRP4 protein (also known as NALP4) was purified from Prevention, and National Institutes of Health. Biosafety in clone U54.M.hNALP4.8 hybridoma supernatant by protein G Microbiological and Biomedical Laboratories. 5th ed. affinity chromatography. The B cell hybridoma was Washington, DC: U.S. Government Printing Office, 2009; see generated by the fusion of P3X63Ag8.653 mouse myeloma www.cdc.gov/biosafety/publications/bmbl5/index.htm. cells with splenocytes from mice immunized by intraperitoneal injection with a truncated recombinant form of Disclaimers: the human NLRP4 protein containing the pyrin domain.1 You are authorized to use this product for research use only.
    [Show full text]
  • 1 Beyond Autoantibodies: Biological Roles of Human Autoreactive B Cells in Rheumatoid Arthritis Revealed by Whole Transcriptome
    bioRxiv preprint doi: https://doi.org/10.1101/144121; this version posted June 1, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Beyond autoantibodies: Biological roles of human autoreactive B cells in rheumatoid arthritis revealed by whole transcriptome profiling. Ankit Mahendra1, Xingyu Yang2, Shaza Abnouf1, Daechan Park3, Sanam Soomro4, Jay RT Adolacion1, Jason Roszik5, Cristian Coarfa6, Gabrielle Romain1, Keith Wanzeck7, S. Louis Bridges Jr.7, Amita Aggarwal8, Peng Qiu2, Sandeep Krishna Agarwal9, Chandra Mohan4, Navin Varadarajan1 Author affiliations 1. Department of Chemical & Biomolecular Engineering, University of Houston, Houston, TX 2. Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 3. Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea 4. Department of Biomedical Engineering, University of Houston, Houston, TX 5. Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 6. Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX 7. Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL 8. Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India 9. Section of Immunology, Allergy and Immunology, Department of Medicine, Baylor College of Medicine, Houston, TX Address for correspondence: Dr. Navin Varadarajan ([email protected]) 1 bioRxiv preprint doi: https://doi.org/10.1101/144121; this version posted June 1, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.
    [Show full text]
  • NOD-Like Receptors (Nlrs) and Inflammasomes
    International Edition www.adipogen.com NOD-like Receptors (NLRs) and Inflammasomes In mammals, germ-line encoded pattern recognition receptors (PRRs) detect the presence of pathogens through recognition of pathogen-associated molecular patterns (PAMPs) or endogenous danger signals through the sensing of danger-associated molecular patterns (DAMPs). The innate immune system comprises several classes of PRRs that allow the early detection of pathogens at the site of infection. The membrane-bound toll-like receptors (TLRs) and C-type lectin receptors (CTRs) detect PAMPs in extracellular milieu and endo- somal compartments. TRLs and CTRs cooperate with PRRs sensing the presence of cytosolic nucleic acids, like RNA-sensing RIG-I (retinoic acid-inducible gene I)-like receptors (RLRs; RLHs) or DNA-sensing AIM2, among others. Another set of intracellular sensing PRRs are the NOD-like receptors (NLRs; nucleotide-binding domain leucine-rich repeat containing receptors), which not only recognize PAMPs but also DAMPs. PAMPs FUNGI/PROTOZOA BACTERIA VIRUSES MOLECULES C. albicans A. hydrophila Adenovirus Bacillus anthracis lethal Plasmodium B. brevis Encephalomyo- toxin (LeTx) S. cerevisiae E. coli carditis virus Bacterial pore-forming L. monocytogenes Herpes simplex virus toxins L. pneumophila Influenza virus Cytosolic dsDNA N. gonorrhoeae Sendai virus P. aeruginosa Cytosolic flagellin S. aureus MDP S. flexneri meso-DAP S. hygroscopicus S. typhimurium DAMPs MOLECULES PARTICLES OTHERS DNA Uric acid UVB Extracellular ATP CPPD Mutations R837 Asbestos Cytosolic dsDNA Irritants Silica Glucose Alum Hyaluronan Amyloid-b Hemozoin Nanoparticles FIGURE 1: Overview on PAMPs and DAMPs recognized by NLRs. NOD-like Receptors [NLRs] The intracellular NLRs organize signaling complexes such as inflammasomes and NOD signalosomes.
    [Show full text]