scholarly journals The Cytosolic Sensor cGAS Detects Mycobacterium tuberculosis DNA to Induce Type I Interferons and Activate Autophagy

2015 ◽  
Vol 17 (6) ◽  
pp. 811-819 ◽  
Author(s):  
Robert O. Watson ◽  
Samantha L. Bell ◽  
Donna A. MacDuff ◽  
Jacqueline M. Kimmey ◽  
Elie J. Diner ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Type I Interferons ◽  
Type I

scholarly journals RNA Sensing of Mycobacterium tuberculosis and Its Impact on TB Vaccination Strategies

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 67 ◽  
Author(s):  
Sanne Burkert ◽  
Ralf R. Schumann
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Type I Interferons ◽  
Immune Memory ◽  
Type I ◽  
Effective Prevention ◽  
Vaccination Strategies ◽  
Host Interaction ◽  
Global Threat ◽  
Antigen Presenting ◽  
The Impact

Tuberculosis (TB) is still an important global threat and although the causing organism has been discovered long ago, effective prevention strategies are lacking. Mycobacterium tuberculosis (MTB) is a unique pathogen with a complex host interaction. Understanding the immune responses upon infection with MTB is crucial for the development of new vaccination strategies and therapeutic targets for TB. Recently, it has been proposed that sensing bacterial nucleic acid in antigen-presenting cells via intracellular pattern recognition receptors (PRRs) is a central mechanism for initiating an effective host immune response. Here, we summarize key findings of the impact of mycobacterial RNA sensing for innate and adaptive host immunity after MTB infection, with emphasis on endosomal toll-like receptors (TLRs) and cytosolic sensors such as NLRP3 and RLRs, modulating T-cell differentiation through IL-12, IL-21, and type I interferons. Ultimately, these immunological pathways may impact immune memory and TB vaccine efficacy. The novel findings described here may change our current understanding of the host response to MTB and potentially impact clinical research, as well as future vaccination design. In this review, the current state of the art is summarized, and an outlook is given on how progress can be made.

scholarly journals LRRK2 regulates innate immune responses and neuroinflammation during Mycobacterium tuberculosis infection

2019 ◽  
Author(s):  
C.G. Weindel ◽  
S.L. Bell ◽  
T.E. Huntington ◽  
K.J. Vail ◽  
R. Srinivasan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Glial Cells ◽  
Mycobacterial Infection ◽  
Type I Interferons ◽  
Type I ◽  
Innate Immune Responses ◽  
Mycobacterium Tuberculosis Infection ◽  
Inflammatory Molecules ◽  
Multiple Hit ◽  
The Brain

SUMMARYDespite many connections between mutations in leucine-rich repeat kinase 2 (LRRK2) and susceptibility to mycobacterial infection, we know little about its function outside of the brain, where it is studied in the context of Parkinson’s Disease (PD). Here, we report that LRRK2 controls peripheral macrophages and brain-resident glial cells’ ability to respond to and express inflammatory molecules. LRRK2 KO macrophages express elevated basal levels of type I interferons, resulting from defective purine metabolism, mitochondrial damage, and engagement of mitochondrial DNA with the cGAS DNA sensing pathway. While LRRK2 KO mice can control Mycobacterium tuberculosis (Mtb) infection, they exhibit exacerbated lung inflammation and altered activation of glial cells in PD-relevant regions of the brain. These results directly implicate LRRK2 in peripheral immunity and support the “multiple-hit hypothesis” of neurodegenerative disease, whereby infection coupled with genetic defects in LRRK2 create an immune milieu that alters activation of glial cells and may trigger PD.

Author response for "Type I interferons provide additive signals for murine regulatory B cell induction by Schistosoma mansoni eggs"

2018 ◽  
Author(s):  
Katja Obieglo ◽  
Alice Costain ◽  
Lauren M. Webb ◽  
Arifa Ozir‐Fazalalikhan ◽  
Shelia L. Brown ◽  
...  
Keyword(s):  
B Cell ◽  
Type I Interferons ◽  
Author Response ◽  
Type I ◽  
Regulatory B Cell ◽  
Cell Induction

Type I Interferons promote maintenance and function of follicular T helper cells in vitro

2019 ◽  
Author(s):  
S Ehrlich ◽  
K Wild ◽  
M Smits ◽  
K Zoldan ◽  
M Hofmann ◽  
...  
Keyword(s):  
T Helper Cells ◽  
Type I Interferons ◽  
Type I ◽  
T Helper ◽  
Helper Cells ◽  
Follicular T Helper Cells ◽  
And Function

PLASMACYTOID DENDRITIC CELLS FUNCTION IN HIV INFECTION

2008 ◽  
Vol 31 (4) ◽  
pp. 13
Author(s):  
Martin Hyrcza ◽  
Mario Ostrowski ◽  
Sandy Der
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Hiv Infection ◽  
Gene Transcription ◽  
Sendai Virus ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifn

Plasmacytoid dendritic cells (pDCs) are innate immune cells able to produce large quantities of type I interferons (IFN) when activated. Human immunodeficiency virus (HIV)-infected patients show generalized immune dysfunction characterized in part by chronic interferon response. In this study we investigated the role of dendritic cells inactivating and maintaining this response. Specifically we compared the IFN geneactivity in pDCs in response to several viruses and TLR agonists. We hypothesized that 1) the pattern of IFN gene transcription would differ in pDCs treated with HIV than with other agents, and 2) that pDCs from patients from different stages of disease would respond differently to the stimulations. To test these hypotheses, we obtained pDCs from 15 HIV-infected and uninfected individuals and treated freshly isolated pDCs with either HIV (BAL strain), influenza virus (A/PR/8/34), Sendai virus (Cantell strain), TLR7 agonist(imiquimod), or TLR9 agonist (CpG-ODN) for 6h. Type I IFN gene transcription was monitored by real time qPCRfor IFNA1, A2, A5, A6, A8,A17, B1, and E1, and cytokine levels were assayed by Cytometric Bead Arrays forTNF?, IL6, IL8, IL10, IL1?, and IL12p70. pDC function as determined by these two assays showed no difference between HIV-infected and uninfected patients or between patients with early or chronic infection. Specifically, HIV did notinduce type I IFN gene expression, whereas influenza virus, Sendai virus and imiquimod did. Similarly, HIV failed to induce any cytokine release from pDCs in contrast to influenza virus, Sendai virus and imiquimod, which stimulatedrelease of TNF?, IL6, or IL8. Together these results suggest that the reaction of pDCs to HIV virus is quantitatively different from the response to agents such as virus, Sendai virus, and imiquimod. In addition, pDCs from HIV-infected persons have responses similar to pDCs from uninfected donors, suggesting, that the DC function may not be affected by HIV infection.

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