Faculty Opinions recommendation of Mycobacterium tuberculosis triggers host type I IFN signaling to regulate IL-1β production in human macrophages.

2015 ◽  
Author(s):  
Padmini Salgame ◽  
Archana Gopalakrishnan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Type I ◽  
Type I Ifn ◽  
Human Macrophages ◽  
Host Type

scholarly journals Mycobacterium tuberculosis Triggers Host Type I IFN Signaling To Regulate IL-1β Production in Human Macrophages

2011 ◽  
Vol 187 (5) ◽  
pp. 2540-2547 ◽  
Author(s):  
Aleksey Novikov ◽  
Marco Cardone ◽  
Robert Thompson ◽  
Kevin Shenderov ◽  
Kevin D. Kirschman ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Type I ◽  
Type I Ifn ◽  
Human Macrophages ◽  
Host Type

scholarly journals TRIM14 Is a Key Regulator of the Type I IFN Response during Mycobacterium tuberculosis Infection

2020 ◽  
Vol 205 (1) ◽  
pp. 153-167 ◽  
Author(s):  
Caitlyn T. Hoffpauir ◽  
Samantha L. Bell ◽  
Kelsi O. West ◽  
Tao Jing ◽  
Allison R. Wagner ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tuberculosis Infection ◽  
Type I ◽  
Type I Ifn ◽  
Mycobacterium Tuberculosis Infection

scholarly journals Type I interferon signaling mediates Mycobacterium tuberculosis–induced macrophage death

2020 ◽  
Vol 218 (2) ◽  
Author(s):  
Li Zhang ◽  
Xiuju Jiang ◽  
Daniel Pfau ◽  
Yan Ling ◽  
Carl F. Nathan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Critical Role ◽  
Type I ◽  
Type I Ifn ◽  
Paracrine Signaling ◽  
Type I Ifns ◽  
Genome Wide ◽  
Mouse Macrophages ◽  
Definition Of

Macrophages help defend the host against Mycobacterium tuberculosis (Mtb), the major cause of tuberculosis (TB). Once phagocytized, Mtb resists killing by macrophages, replicates inside them, and leads to their death, releasing Mtb that can infect other cells. We found that the death of Mtb-infected mouse macrophages in vitro does not appear to proceed by a currently known pathway. Through genome-wide CRISPR-Cas9 screening, we identified a critical role for autocrine or paracrine signaling by macrophage-derived type I IFNs in the death of Mtb-infected macrophages in vitro, and blockade of type I IFN signaling augmented the effect of rifampin, a first-line TB drug, in Mtb-infected mice. Further definition of the pathway of type I IFN–mediated macrophage death may allow for host-directed therapy of TB that is more selective than systemic blockade of type I IFN signaling.

scholarly journals Transcriptional Profiling of Human Peripheral Blood Mononuclear Cells Stimulated by Mycobacterium tuberculosis PPE57 Identifies Characteristic Genes Associated With Type I Interferon Signaling

2021 ◽  
Vol 11 ◽  
Author(s):  
Fanli Yi ◽  
Jing Hu ◽  
Xiaoyan Zhu ◽  
Yue Wang ◽  
Qiuju Yu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Glutamic Acid ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Type I ◽  
Type I Ifn ◽  
Rna Seq ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Proline-glutamic acid (PE)- and proline-proline-glutamic acid (PPE)-containing proteins are exclusive to Mycobacterium tuberculosis (MTB), the leading cause of tuberculosis (TB). In this study, we performed global transcriptome sequencing (RNA-Seq) on PPE57-stimulated peripheral blood mononuclear cells (PBMCs) and control samples to quantitatively measure the expression level of key transcripts of interest. A total of 1367 differentially expressed genes (DEGs) were observed in response to a 6 h exposure to PPE57, with 685 being up-regulated and 682 down-regulated. Immune-related gene functions and pathways associated with these genes were evaluated, revealing that the type I IFN signaling pathway was the most significantly enriched pathway in our RNA-seq dataset, with 14 DEGs identified therein including ISG15, MX2, IRF9, IFIT3, IFIT2, OAS3, IFIT1, IFI6, OAS2, OASL, RSAD2, OAS1, IRF7, and MX1. These PPE57-related transcriptomic profiles have implications for a better understanding of host global immune mechanisms underlying MTB infection outcomes. However, more studies regarding these DEGs and type I IFN signaling in this infectious context are necessary to more fully clarify the underlying mechanisms that arise in response to PPE57 during MTB infection.

scholarly journals PARP1 Enhances Influenza A Virus Propagation by Facilitating Degradation of Host Type I Interferon Receptor

2020 ◽  
Vol 94 (7) ◽  
Author(s):  
Chuan Xia ◽  
Jennifer J. Wolf ◽  
Chuankai Sun ◽  
Mengqiong Xu ◽  
Caleb J. Studstill ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Influenza Virus ◽  
Molecular Mechanism ◽  
Influenza A Virus ◽  
Influenza A ◽  
Type I Interferon ◽  
Type I ◽  
Type I Ifn ◽  
Host Type ◽  
Host Innate Immunity

ABSTRACT Influenza A virus (IAV) utilizes multiple strategies to confront or evade host type I interferon (IFN)-mediated antiviral responses in order to enhance its own propagation within the host. One such strategy is to induce the degradation of type I IFN receptor 1 (IFNAR1) by utilizing viral hemagglutinin (HA). However, the molecular mechanism behind this process is poorly understood. Here, we report that a cellular protein, poly(ADP-ribose) polymerase 1 (PARP1), plays a critical role in mediating IAV HA-induced degradation of IFNAR1. We identified PARP1 as an interacting partner for IAV HA through mass spectrometry analysis. This interaction was confirmed by coimmunoprecipitation analyses. Furthermore, confocal fluorescence microscopy showed altered localization of endogenous PARP1 upon transient IAV HA expression or during IAV infection. Knockdown or inhibition of PARP1 rescued IFNAR1 levels upon IAV infection or HA expression, exemplifying the importance of PARP1 for IAV-induced reduction of IFNAR1. Notably, PARP1 was crucial for the robust replication of IAV, which was associated with regulation of the type I IFN receptor signaling pathway. These results indicate that PARP1 promotes IAV replication by controlling viral HA-induced degradation of host type I IFN receptor. Altogether, these findings provide novel insight into interactions between influenza virus and the host innate immune response and reveal a new function for PARP1 during influenza virus infection. IMPORTANCE Influenza A virus (IAV) infections cause seasonal and pandemic influenza outbreaks, which pose a devastating global health concern. Despite the availability of antivirals against influenza, new IAV strains continue to persist by overcoming the therapeutics. Therefore, much emphasis in the field is placed on identifying new therapeutic targets that can more effectively control influenza. IAV utilizes several tactics to evade host innate immunity, which include the evasion of antiviral type I interferon (IFN) responses. Degradation of type I IFN receptor (IFNAR) is one known method of subversion, but the molecular mechanism for IFNAR downregulation during IAV infection remains unclear. Here, we have found that a host protein, poly(ADP-ribose) polymerase 1 (PARP1), facilitates IFNAR degradation and accelerates IAV replication. The findings reveal a novel cellular target for the potential development of antivirals against influenza, as well as expand our base of knowledge regarding interactions between influenza and the host innate immunity.

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