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  1. Article ; Online: Transgenic mouse models support a protective role of type I IFN response in SARS-CoV-2 infection-related lung immunopathology and neuroinvasion.

    Chauhan, Nishant Ranjan / Kundu, Soumya / Bal, Ramyasingh / Chattopadhyay, Diya / Sahu, Rinku / Mehto, Subhash / Yadav, Rina / Krishna, Sivaram / Jena, Kautilya Kumar / Satapathy, Sameekshya / Pv, Anusha / Murmu, Krushna C / Singh, Bharati / Patnaik, Srinivas / Jena, Sarita / Harshan, Krishnan H / Syed, Gulam Hussain / Idris, Mohammed M / Prasad, Punit /
    Chauhan, Santosh

    Cell reports

    2023  Volume 42, Issue 11, Page(s) 113275

    Abstract: Type I interferon (IFN-I) response is the first line of host defense against invading viruses. In the absence of definite mouse models, the role of IFN-I in SARS-CoV-2 infection remains perplexing. Here, we develop two mouse models, one with ... ...

    Abstract Type I interferon (IFN-I) response is the first line of host defense against invading viruses. In the absence of definite mouse models, the role of IFN-I in SARS-CoV-2 infection remains perplexing. Here, we develop two mouse models, one with constitutively high IFN-I response (hACE2; Irgm1
    MeSH term(s) Mice ; Animals ; Mice, Transgenic ; COVID-19 ; SARS-CoV-2 ; Interferon Type I ; Mice, Knockout ; Antibodies ; Disease Models, Animal ; Lung
    Chemical Substances Interferon Type I ; Antibodies
    Language English
    Publishing date 2023-10-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.113275
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses.

    Nath, Parej / Chauhan, Nishant Ranjan / Jena, Kautilya Kumar / Datey, Ankita / Kumar, Nilima Dinesh / Mehto, Subhash / De, Saikat / Nayak, Tapas Kumar / Priyadarsini, Swatismita / Rout, Kshitish / Bal, Ramyasingh / Murmu, Krushna C / Kalia, Manjula / Patnaik, Srinivas / Prasad, Punit / Reggiori, Fulvio / Chattopadhyay, Soma / Chauhan, Santosh

    EMBO reports

    2021  Volume 22, Issue 11, Page(s) e52948

    Abstract: The type I interferon (IFN) response is the major host arsenal against invading viruses. IRGM is a negative regulator of IFN responses under basal conditions. However, the role of human IRGM during viral infection has remained unclear. In this study, we ... ...

    Abstract The type I interferon (IFN) response is the major host arsenal against invading viruses. IRGM is a negative regulator of IFN responses under basal conditions. However, the role of human IRGM during viral infection has remained unclear. In this study, we show that IRGM expression is increased upon viral infection. IFN responses induced by viral PAMPs are negatively regulated by IRGM. Conversely, IRGM depletion results in a robust induction of key viral restriction factors including IFITMs, APOBECs, SAMHD1, tetherin, viperin, and HERC5/6. Additionally, antiviral processes such as MHC-I antigen presentation and stress granule signaling are enhanced in IRGM-deficient cells, indicating a robust cell-intrinsic antiviral immune state. Consistently, IRGM-depleted cells are resistant to the infection with seven viruses from five different families, including Togaviridae, Herpesviridae, Flaviviverdae, Rhabdoviridae, and Coronaviridae. Moreover, we show that Irgm1 knockout mice are highly resistant to chikungunya virus (CHIKV) infection. Altogether, our work highlights IRGM as a broad therapeutic target to promote defense against a large number of human viruses, including SARS-CoV-2, CHIKV, and Zika virus.
    MeSH term(s) Animals ; Antiviral Agents/pharmacology ; GTP-Binding Proteins/antagonists & inhibitors ; Humans ; Mice ; Virus Diseases/immunology ; Virus Replication
    Chemical Substances Antiviral Agents ; GTP-Binding Proteins (EC 3.6.1.-) ; IRGM protein, human (EC 3.6.1.-)
    Language English
    Publishing date 2021-09-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.202152948
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5433: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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    Zs.MG 41: Show issues

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  3. Article ; Online: Selective autophagy of RIPosomes maintains innate immune homeostasis during bacterial infection.

    Mehto, Subhash / Jena, Kautilya Kumar / Yadav, Rina / Priyadarsini, Swatismita / Samal, Pallavi / Krishna, Sivaram / Dhar, Kollori / Jain, Ashish / Chauhan, Nishant Ranjan / Murmu, Krushna C / Bal, Ramyasingh / Sahu, Rinku / Jaiswal, Pundrik / Sahoo, Bhabani Sankar / Patnaik, Srinivas / Kufer, Thomas A / Rusten, Tor Erik / Chauhan, Swati / Prasad, Punit /
    Chauhan, Santosh

    The EMBO journal

    2022  Volume 41, Issue 23, Page(s) e111289

    Abstract: The NOD1/2-RIPK2 is a key cytosolic signaling complex that activates NF-κB pro-inflammatory response against invading pathogens. However, uncontrolled NF-κB signaling can cause tissue damage leading to chronic diseases. The mechanisms by which the NODs- ... ...

    Abstract The NOD1/2-RIPK2 is a key cytosolic signaling complex that activates NF-κB pro-inflammatory response against invading pathogens. However, uncontrolled NF-κB signaling can cause tissue damage leading to chronic diseases. The mechanisms by which the NODs-RIPK2-NF-κB innate immune axis is activated and resolved remain poorly understood. Here, we demonstrate that bacterial infection induces the formation of endogenous RIPK2 oligomers (RIPosomes) that are self-assembling entities that coat the bacteria to induce NF-κB response. Next, we show that autophagy proteins IRGM and p62/SQSTM1 physically interact with NOD1/2, RIPK2 and RIPosomes to promote their selective autophagy and limit NF-κB activation. IRGM suppresses RIPK2-dependent pro-inflammatory programs induced by Shigella and Salmonella. Consistently, the therapeutic inhibition of RIPK2 ameliorates Shigella infection- and DSS-induced gut inflammation in Irgm1 KO mice. This study identifies a unique mechanism where the innate immune proteins and autophagy machinery are recruited together to the bacteria for defense as well as for maintaining immune homeostasis.
    MeSH term(s) Mice ; Animals ; NF-kappa B/metabolism ; Mice, Inbred NOD ; Bacterial Infections ; Autophagy ; Immunity, Innate ; Homeostasis
    Chemical Substances NF-kappa B
    Language English
    Publishing date 2022-10-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 586044-1
    ISSN 1460-2075 ; 0261-4189
    ISSN (online) 1460-2075
    ISSN 0261-4189
    DOI 10.15252/embj.2022111289
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1808: Show issues Location:
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  4. Article ; Online: Transgenic Mouse Models Establish a Protective Role of Type 1 IFN Response in SARS-CoV-2 infection-related Immunopathology

    Chauhan, Nishant Ranjan / Kundu, Soumya / Bal, Ramyasingh / Chattopadhyay, Diya / Mehto, Subhash / Sahu, Rinku / Yadav, Rina / Krishna, Sivaram / Jena, Kautilya Kumar / Satapathy, Sameekshya / Murmu, Krushna C. / Singh, Bharati / Das, Saroj Kumar / Jena, Sarita / Harshan, Krishnan H. / Syed, Gulam Hussain / Prasad, Punit / Chauhan, Santosh

    bioRxiv

    Abstract: Type 1 interferon (IFN-I) response is the first line of host defense against invading viruses. In the absence of definite mouse models, however, the role of IFN-I in SARS-CoV-2 infections remained to be perplexing. Here, we developed two mouse models, ... ...

    Abstract Type 1 interferon (IFN-I) response is the first line of host defense against invading viruses. In the absence of definite mouse models, however, the role of IFN-I in SARS-CoV-2 infections remained to be perplexing. Here, we developed two mouse models, one with constitutively high IFN-I response (hACE2; Irgm1-/-) and the other with dampened IFN-I response (hACE2; Ifnar1-/-) to comprehend the role of IFN-I response during SARS-CoV-2 invasion. We found that hACE2; Irgm1-/- mice were resistant to lethal SARS-CoV-2 (including delta variant) infection with substantially reduced cytokine storm and immunopathology in the lungs and brain. In striking contrast, a severe SARS-CoV-2 infection along with immune cell infiltration, inflammatory response, and enhanced pathology was observed in the lungs of hACE2; Ifnar1-/- mice. Additionally, hACE2; Ifnar1-/- mice were highly susceptible to SARS-CoV-2 neuroinvasion in the brain accompanied by immune cell infiltration, microglia/astrocytes activation, cytokine response, and demyelination of neurons. The hACE2; Irgm1-/- Ifnar1-/- double knockout mice or hACE2; Irgm1-/- mice treated with STING or RIPK2 pharmacological inhibitors displayed loss of the protective phenotypes observed in hACE2; Irgm1-/- mice suggesting that heightened IFN-I response accounts for the observed immunity. Taken together, we explicitly demonstrate that IFN-I protects from lethal SARS-CoV-2 infection, and Irgm1 (IRGM) could be an excellent therapeutic target against COVID-19.
    Keywords covid19
    Language English
    Publishing date 2022-12-19
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2022.12.17.520843
    Database COVID19

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  5. Article ; Online: Autoimmunity gene IRGM suppresses cGAS-STING and RIG-I-MAVS signaling to control interferon response.

    Jena, Kautilya Kumar / Mehto, Subhash / Nath, Parej / Chauhan, Nishant Ranjan / Sahu, Rinku / Dhar, Kollori / Das, Saroj Kumar / Kolapalli, Srinivasa Prasad / Murmu, Krushna C / Jain, Ashish / Krishna, Sivaram / Sahoo, Bhabani Sankar / Chattopadhyay, Soma / Rusten, Tor Erik / Prasad, Punit / Chauhan, Swati / Chauhan, Santosh

    EMBO reports

    2020  Volume 21, Issue 9, Page(s) e50051

    Abstract: Activation of the type 1 interferon response is extensively connected to the pathogenesis of autoimmune diseases. Loss of function of Immunity Related GTPase M (IRGM) has also been associated to several autoimmune diseases, but its mechanism of action is ...

    Abstract Activation of the type 1 interferon response is extensively connected to the pathogenesis of autoimmune diseases. Loss of function of Immunity Related GTPase M (IRGM) has also been associated to several autoimmune diseases, but its mechanism of action is unknown. Here, we found that IRGM is a master negative regulator of the interferon response. Several nucleic acid-sensing pathways leading to interferon-stimulated gene expression are highly activated in IRGM knockout mice and human cells. Mechanistically, we show that IRGM interacts with nucleic acid sensor proteins, including cGAS and RIG-I, and mediates their p62-dependent autophagic degradation to restrain interferon signaling. Further, IRGM deficiency results in defective mitophagy leading to the accumulation of defunct leaky mitochondria that release cytosolic DAMPs and mtROS. Hence, IRGM deficiency increases not only the levels of the sensors, but also those of the stimuli that trigger the activation of the cGAS-STING and RIG-I-MAVS signaling axes, leading to robust induction of IFN responses. Taken together, this study defines the molecular mechanisms by which IRGM maintains interferon homeostasis and protects from autoimmune diseases.
    MeSH term(s) Animals ; Autoimmune Diseases/genetics ; Autoimmunity/genetics ; Autophagy ; Mice ; Nucleotidyltransferases/genetics ; Nucleotidyltransferases/metabolism ; Signal Transduction
    Chemical Substances Nucleotidyltransferases (EC 2.7.7.-)
    Language English
    Publishing date 2020-07-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.202050051
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5433: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 41: Show issues

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