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https://www.readbyqxmd.com/read/29150429/cgamp-a-tale-of-two-signals
#1
Teneema Kuriakose, Thirumala-Devi Kanneganti
In this issue of JEM, Swanson et al. (https://doi.org/10.1084/jem.20171749) report an unanticipated role for cGAMP in priming and activation of inflammasomes in addition to its well-characterized function as an endogenous second messenger inducing type I interferons in the cytosolic DNA-sensing pathway.
November 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29128729/recent-advances-in-inflammasome-biology
#2
REVIEW
David E Place, Thirumala-Devi Kanneganti
The inflammasome is a complex of proteins that through the activity of caspase-1 and the downstream substrates gasdermin D, IL-1β, and IL-18 execute an inflammatory form of cell death termed pyroptosis. Activation of this complex often involves the adaptor protein ASC and upstream sensors including NLRP1, NLRP3, NLRC4, AIM2, and pyrin, which are activated by different stimuli including infectious agents and changes in cell homeostasis. Here we discuss new regulatory mechanisms that have been identified for the canonical inflammasomes, the most recently identified NLRP9b inflammasome, and the new gasdermin family of proteins that mediate pyroptosis and other forms of regulated cell death...
November 9, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29027223/inflammatory-cell-death-in-intestinal-pathologies
#3
REVIEW
Deepika Sharma, Thirumala-Devi Kanneganti
The intestinal tract is a site of intense immune cell activity that is poised to mount an effective response against a pathogen and yet maintain tolerance toward commensal bacteria and innocuous dietary antigens. The role of cell death in gut pathologies is particularly important as the intestinal epithelium undergoes self-renewal every 4-7 days through a continuous process of cell death and cell division. Cell death is also required for removal of infected, damaged, and cancerous cells. Certain forms of cell death trigger inflammation through release of damage-associated molecular patterns...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28974614/inflammasome-activation-by-bacterial-outer-membrane-vesicles-requires-guanylate-binding-proteins
#4
Ryan Finethy, Sarah Luoma, Nichole Orench-Rivera, Eric M Feeley, Arun K Haldar, Masahiro Yamamoto, Thirumala-Devi Kanneganti, Meta J Kuehn, Jörn Coers
The Gram-negative bacterial cell wall component lipopolysaccharide (LPS) is recognized by the noncanonical inflammasome protein caspase-11 in the cytosol of infected host cells and thereby prompts an inflammatory immune response linked to sepsis. Host guanylate binding proteins (GBPs) promote infection-induced caspase-11 activation in tissue culture models, and yet their in vivo role in LPS-mediated sepsis has remained unexplored. LPS can be released from lysed bacteria as "free" LPS aggregates or actively secreted by live bacteria as a component of outer membrane vesicles (OMVs)...
October 3, 2017: MBio
https://www.readbyqxmd.com/read/28947539/priming-and-activation-of-inflammasome-by-canarypox-virus-vector-alvac-via-the-cgas-ifi16-sting-type-i-ifn-pathway-and-aim2-sensor
#5
Fengliang Liu, Qingli Niu, Xiuzhen Fan, Connie Liu, Jie Zhang, Zhi Wei, Wei Hou, Thirumala-Devi Kanneganti, Merlin L Robb, Jerome H Kim, Nelson L Michael, Jiaren Sun, Lynn Soong, Haitao Hu
Viral vectors derived from different virus families, including poxvirus (canarypox virus vector ALVAC) and adenovirus (human Ad5 vector), have been widely used in vaccine development for a range of human diseases including HIV/AIDS. Less is known about the mechanisms underlying the host innate response to these vectors. Increasing evidence from clinical vaccine trials testing different viral vectors has suggested the importance of understanding basic elements of host-viral vector interactions. In this study, we investigated the innate interactions of APCs with two commonly used HIV vaccine vectors, ALVAC and Ad5, and identified AIM2 as an innate sensor for ALVAC, triggering strong inflammasome activation in both human and mouse APCs...
November 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28904353/toll-like-receptor%C3%A2-2-induced-cytotoxic-t-lymphocyte-associated-protein%C3%A2-4-regulates-aspergillus-induced-regulatory-t-cells-with-pro-inflammatory-characteristics
#6
Ruud P H Raijmakers, Evelien G G Sprenkeler, Floor E Aleva, Cor W M Jacobs, Thirumala-Devi Kanneganti, Leo A B Joosten, Frank L van de Veerdonk, Mark S Gresnigt
Patients with cystic fibrosis, chronic obstructive pulmonary disease, severe asthma, pre-existing pulmonary lesions, and severely immunocompromised patients are susceptible to develop infections with the opportunistic pathogenic fungus Aspergillus fumigatus, called aspergillosis. Infections in these patients are associated with persistent pro-inflammatory T-helper (TH)2 and TH17 responses. Regulatory T-cells, natural suppressor cells of the immune system, control pro-inflammatory T-cell responses, but can also contribute to disease by shifting to a pro-inflammatory TH17-like phenotype...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28813221/inflammatory-bowel-disease-and-the-nlrp3-inflammasome
#7
Thirumala-Devi Kanneganti
New England Journal of Medicine, Volume 377, Issue 7, Page 694-696, August 2017.
August 17, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28783694/zbp1-dai-is-an-innate-sensor-of-influenza-virus-triggering-the-nlrp3-inflammasome-and-programmed-cell-death-pathways
#8
Teneema Kuriakose, Si Ming Man, R K Subbarao Malireddi, Rajendra Karki, Sannula Kesavardhana, David E Place, Geoffrey Neale, Peter Vogel, Thirumala-Devi Kanneganti
The interferon (IFN)-inducible protein Z-DNA binding protein 1 [ZBP1; also known as DNA-dependent activator of IFN regulatory factors (DAI) and DLM-1] was identified as a double-stranded DNA sensor, which instigates innate immune responses. However, this classification has been disputed, and whether ZBP1 functions as a pathogen sensor during an infection has remained unknown. We demonstrated ZBP1-mediated sensing of the influenza A virus (IAV) proteins NP and PB1, triggering cell death and inflammatory responses via the receptor-interacting protein kinase 1 (RIPK1)-RIPK3-caspase-8 axis...
August 12, 2016: Science Immunology
https://www.readbyqxmd.com/read/28704655/war-on-viruses-lc3-recruits-gtpases
#9
Teneema Kuriakose, Thirumala-Devi Kanneganti
Interferon effector functions and autophagy are evolutionarily conserved arms of cell-autonomous immunity that restrict replication of intracellular pathogens. In this issue of Cell Host and Microbe, Biering et al., (2017) demonstrate how host cells co-opt sequential action of autophagy proteins and IFN-inducible GTPases to inhibit replication of positive-sense RNA viruses.
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28634194/zbp1-dai-ubiquitination-and-sensing-of-influenza-vrnps-activate-programmed-cell-death
#10
Sannula Kesavardhana, Teneema Kuriakose, Clifford S Guy, Parimal Samir, R K Subbarao Malireddi, Ashutosh Mishra, Thirumala-Devi Kanneganti
Innate sensing of influenza virus infection induces activation of programmed cell death pathways. We have recently identified Z-DNA-binding protein 1 (ZBP1) as an innate sensor of influenza A virus (IAV). ZBP1-mediated IAV sensing is critical for triggering programmed cell death in the infected lungs. Surprisingly, little is known about the mechanisms regulating ZBP1 activation to induce programmed cell death. Here, we report that the sensing of IAV RNA by retinoic acid inducible gene I (RIG-I) initiates ZBP1-mediated cell death via the RIG-I-MAVS-IFN-β signaling axis...
August 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28615208/deficiency-of-the-nod-like-receptor-nlrc5-results-in-decreased-cd8-t-cell-function-and-impaired-viral-clearance
#11
Christopher R Lupfer, Kate L Stokes, Teneema Kuriakose, Thirumala-Devi Kanneganti
Pathogen recognition receptors are vital components of the immune system. Engagement of these receptors is important not only for instigation of innate immune responses to invading pathogens but also for initiating the adaptive immune response. Members of the NOD-like receptor (NLR) family of pathogen recognition receptors have important roles in orchestrating this response. The NLR family member NLRC5 regulates major histocompatibility complex class I (MHC-I) expression during various types of infections, but its role in immunity to influenza A virus (IAV) is not well studied...
September 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28598238/nlrc3-regulates-cellular-proliferation-and-apoptosis-to-attenuate-the-development-of-colorectal-cancer
#12
Rajendra Karki, R K Subbarao Malireddi, Qifan Zhu, Thirumala-Devi Kanneganti
Nucleotide-binding domain, leucine-rich-repeat-containing proteins (NLRs) are intracellular innate immune sensors of pathogen-associated and damage-associated molecular patterns. NLRs regulate diverse biologic processes such as inflammatory responses, cell proliferation and death, and gut microbiota to attenuate tumorigenesis. In a recent publication in Nature, we identified NLRC3 as a negative regulator of PI3K-mTOR signaling and characterized its potential tumor suppressor function. Enterocytes lacking NLRC3 cannot control cellular proliferation because they are unable to suppress activation of PI3K-mTOR signaling pathways...
July 3, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28531279/mechanisms-governing-inflammasome-activation-assembly-and-pyroptosis-induction
#13
Sannula Kesavardhana, Thirumala-Devi Kanneganti
Inflammasomes are multimeric protein complexes that regulate inflammatory responses and pyroptotic cell death to exert host defense against microbes. Intracellular pattern-recognition receptors such as nucleotide-binding domain and leucine-rich repeat receptors (NLRs) and absent in melanoma 2 like receptors (ALRs) assemble the inflammasome complexes in response to pathogens and danger or altered-self signals in the cell. Inflammasome sensors, in association with an adaptor protein-apoptosis-associated speck-like protein containing a caspase-activation and -recruitment domain (ASC)-activate inflammatory caspase-1 to enable the release of inflammatory cytokines and induce cell death, conferring host defense against pathogens...
May 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28468974/cutting-edge-distinct-regulatory-mechanisms-control-proinflammatory-cytokines-il-18-and-il-1%C3%AE
#14
Qifan Zhu, Thirumala-Devi Kanneganti
Interleukin-18 and IL-1β, which are cytokines of the IL-1 family, are synthesized as precursor proteins and activated by the inflammasome via proteolytic processing. IL-1β is only induced in response to inflammatory stimuli, but IL-18 is constitutively expressed. However, how IL-18 and IL-1β expression is regulated by different inflammatory signals remains poorly studied. In this study, we found that IL-18 and IL-1β are differentially regulated. Despite being constitutively expressed, IL-18 expression was increased and sustained after stimulation of TLRs...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28462526/molecular-mechanisms-and-functions-of-pyroptosis-inflammatory-caspases-and-inflammasomes-in-infectious-diseases
#15
REVIEW
Si Ming Man, Rajendra Karki, Thirumala-Devi Kanneganti
Cell death is a fundamental biological phenomenon that is essential for the survival and development of an organism. Emerging evidence also indicates that cell death contributes to immune defense against infectious diseases. Pyroptosis is a form of inflammatory programmed cell death pathway activated by human and mouse caspase-1, human caspase-4 and caspase-5, or mouse caspase-11. These inflammatory caspases are used by the host to control bacterial, viral, fungal, or protozoan pathogens. Pyroptosis requires cleavage and activation of the pore-forming effector protein gasdermin D by inflammatory caspases...
May 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28410990/tyrosine-kinase-syk-licenses-myd88-adaptor-protein-to-instigate-il-1%C3%AE-mediated-inflammatory-disease
#16
Prajwal Gurung, Gaofeng Fan, John R Lukens, Peter Vogel, Nicholas K Tonks, Thirumala-Devi Kanneganti
Mice carrying a hypomorphic point mutation in the Ptpn6 gene (Ptpn6(spin) mice) develop an inflammatory skin disease that resembles neutrophilic dermatosis in humans. Here, we demonstrated that interleukin-1α (IL-1α) signaling through IL-1R and MyD88 in both stromal and immune cells drive inflammation in Ptpn6(spin) mice. We further identified SYK as a critical kinase that phosphorylates MyD88, promoted MyD88-dependent signaling and mediates dermatosis in Ptpn6(spin) mice. Our studies further demonstrated that SHP1 encoded by Ptpn6 binds and suppresses SYK activation to inhibit MyD88 phosphorylation...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28374568/inflammasome-activation-by-nucleic-acids-and-nucleosomes-in-sterile-inflammation%C3%A2-or-is-it-sterile
#17
REVIEW
Christopher R Lupfer, Angeline Rodriguez, Thirumala-Devi Kanneganti
Inflammasomes are multiprotein complexes that form in the cytoplasm in response to cellular damage and cytosolic pathogen-associated molecules during infection. These complexes play important roles in initiating innate and adaptive immune responses to infectious disease. In addition, inflammasomes are now recognized as important mediators of sterile inflammation in various autoimmune and autoinflammatory diseases. Interestingly, microbiota and infection play critical roles in the development of 'sterile inflammation'...
August 2017: FEBS Journal
https://www.readbyqxmd.com/read/28345580/differential-roles-of-caspase-1-and-caspase-11-in-infection-and-inflammation
#18
Si Ming Man, Rajendra Karki, Benoit Briard, Amanda Burton, Sebastien Gingras, Stephane Pelletier, Thirumala-Devi Kanneganti
Caspase-1, also known as interleukin-1β (IL-1β)-converting enzyme (ICE), regulates antimicrobial host defense, tissue repair, tumorigenesis, metabolism and membrane biogenesis. On activation within an inflammasome complex, caspase-1 induces pyroptosis and converts pro-IL-1β and pro-IL-18 into their biologically active forms. "ICE(-/-)" or "Casp1(-/-)" mice generated using 129 embryonic stem cells carry a 129-associated inactivating passenger mutation on the caspase-11 locus, essentially making them deficient in both caspase-1 and caspase-11...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28169000/regulation-and-functions-of-nlrp3-inflammasome-during-influenza-virus-infection
#19
Teneema Kuriakose, Thirumala-Devi Kanneganti
The NLRP3 inflammasome constitutes a major antiviral host defense mechanism during influenza virus infection. Inflammasome assembly in virus-infected cells facilitates autocatalytic processing of pro-caspase-1 and subsequent cleavage and secretion of proinflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome is critical for induction of both innate and adaptive immune responses during influenza virus infection. Inflammasome-dependent antiviral responses also regulate immunopathology and tissue repair in the infected lungs...
June 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28130494/oxidized-low-density-lipoprotein-immune-complex-priming-of-the-nlrp3-inflammasome-involves-tlr-and-fc%C3%AE-r-cooperation-and-is-dependent-on-card9
#20
Jillian P Rhoads, John R Lukens, Ashley J Wilhelm, Jared L Moore, Yanice Mendez-Fernandez, Thirumala-Devi Kanneganti, Amy S Major
Oxidized low-density lipoprotein (oxLDL) is known to activate inflammatory responses in a variety of cells, especially macrophages and dendritic cells. Interestingly, much of the oxLDL in circulation is complexed to Abs, and these resulting immune complexes (ICs) are a prominent feature of chronic inflammatory disease, such as atherosclerosis, type-2 diabetes, systemic lupus erythematosus, and rheumatoid arthritis. Levels of oxLDL ICs often correlate with disease severity, and studies demonstrated that oxLDL ICs elicit potent inflammatory responses in macrophages...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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