scholarly journals A negative feedback loop of ICER and NF-κB regulates TLR signaling in innate immune responses

2016 ◽  
Vol 24 (3) ◽  
pp. 492-499 ◽  
Author(s):  
Sihan Lv ◽  
Jian Li ◽  
Xinchen Qiu ◽  
Weida Li ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Innate Immune ◽  
Negative Feedback Loop ◽  
Innate Immune Responses ◽  
Tlr Signaling

A Negative Feedback Loop Between Autophagy and Immune Responses in Mycobacterium leprae Infection

2017 ◽  
Vol 36 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Yuelong Ma ◽  
Li Zhang ◽  
Jie Lu ◽  
Tiejun Shui ◽  
Jia Chen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Mycobacterium Leprae ◽  
Negative Feedback Loop

scholarly journals Absence of Non-Canonical, Inhibitory MYD88 Splice Variants in B Cell Lymphomas Correlates With Sustained NF-κB Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Yamel Cardona Gloria ◽  
Stephan H. Bernhart ◽  
Sven Fillinger ◽  
Olaf-Oliver Wolz ◽  
Sabine Dickhöfer ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
B Cells ◽  
B Cell ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Splice Variants ◽  
Myeloid Cells ◽  
Negative Feedback Loop ◽  
Tlr Signaling ◽  
Splice Isoforms

Gain-of-function mutations of the TLR adaptor and oncoprotein MyD88 drive B cell lymphomagenesis via sustained NF-κB activation. In myeloid cells, both short and sustained TLR activation and NF-κB activation lead to the induction of inhibitory MYD88 splice variants that restrain prolonged NF-κB activation. We therefore sought to investigate whether such a negative feedback loop exists in B cells. Analyzing MYD88 splice variants in normal B cells and different primary B cell malignancies, we observed that MYD88 splice variants in transformed B cells are dominated by the canonical, strongly NF-κB-activating isoform of MYD88 and contain at least three novel, so far uncharacterized signaling-competent splice isoforms. Sustained TLR stimulation in B cells unexpectedly reinforces splicing of NF-κB-promoting, canonical isoforms rather than the ‘MyD88s’, a negative regulatory isoform reported to be typically induced by TLRs in myeloid cells. This suggests that an essential negative feedback loop restricting TLR signaling in myeloid cells at the level of alternative splicing, is missing in B cells when they undergo proliferation, rendering B cells vulnerable to sustained NF-κB activation and eventual lymphomagenesis. Our results uncover MYD88 alternative splicing as an unappreciated promoter of B cell lymphomagenesis and provide a rationale why oncogenic MYD88 mutations are exclusively found in B cells.

scholarly journals Innate immune responses after stimulation with Toll-like receptor agonists in ex vivo microglial cultures and an in vivo model using mice with reduced microglia

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
James A. Carroll ◽  
Brent Race ◽  
Katie Williams ◽  
James F. Striebel ◽  
Bruce Chesebro
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Ex Vivo ◽  
Innate Immune ◽  
Cpg Odn ◽  
Innate Immune Responses ◽  
Tlr Signaling ◽  
Tlr Agonists ◽  
Tlr7 Agonist

Abstract Background Past experiments studying innate immunity in the central nervous system (CNS) utilized microglia obtained from neonatal mouse brain, which differ developmentally from adult microglia. These differences might impact our current understanding of the role of microglia in CNS development, function, and disease. Methods Cytokine protein secretion was compared in ex vivo P3 and adult microglial cultures after exposure to agonists for three different toll-like receptors (TLR4, lipopolysaccharide [LPS]; TLR7, imiquimod [IMQ]; and TLR9, CpG Oligodeoxynucleotide [CpG-ODN] 1585). In addition, changes in inflammatory gene expression in ex vivo adult microglia in response to the TLR agonists was assessed. Furthermore, in vivo experiments evaluated changes in gene expression associated with inflammation and TLR signaling in brains of mice with or without treatment with PLX5622 to reduce microglia. Results Ex vivo adult and P3 microglia increased cytokine secretion when exposed to TLR4 agonist LPS and to TLR7 agonist IMQ. However, adult microglia decreased expression of numerous genes after exposure to TLR 9 agonist CpG-ODN 1585. In contrast, in vivo studies indicated a core group of inflammatory and TLR signaling genes increased when each of the TLR agonists was introduced into the CNS. Reducing microglia in the brain led to decreased expression of various inflammatory and TLR signaling genes. Mice with reduced microglia showed extreme impairment in upregulation of genes after exposure to TLR7 agonist IMQ. Conclusions Cultured adult microglia were more reactive than P3 microglia to LPS or IMQ exposure. In vivo results indicated microglial influences on neuroinflammation were agonist specific, with responses to TLR7 agonist IMQ more dysregulated in mice with reduced microglia. Thus, TLR7-mediated innate immune responses in the CNS appeared more dependent on the presence of microglia. Furthermore, partial responses to TLR4 and TLR9 agonists in mice with reduced microglia suggested other cell types in the CNS can compensate for their absence.

scholarly journals Nod1/RICK and TLR Signaling Regulate Chemokine and Antimicrobial Innate Immune Responses in Mesothelial Cells

2007 ◽  
Vol 179 (1) ◽  
pp. 514-521 ◽  
Author(s):  
Jong-Hwan Park ◽  
Yun-Gi Kim ◽  
Michael Shaw ◽  
Thirumala-Devi Kanneganti ◽  
Yukari Fujimoto ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mesothelial Cells ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Tlr Signaling

COMPLEX DYNAMICAL ANALYSIS OF A COUPLED NETWORK FROM INNATE IMMUNE RESPONSES

2013 ◽  
Vol 23 (11) ◽  
pp. 1350180 ◽  
Author(s):  
JINYING TAN ◽  
XIUFEN ZOU
Keyword(s):  
Immune Responses ◽  
Negative Feedback ◽  
Equilibrium Points ◽  
Dynamical Behavior ◽  
Innate Immune ◽  
Dynamical Analysis ◽  
Innate Immune Responses ◽  
Dynamical Behaviors ◽  
Positive And Negative Feedback ◽  
The Stability

In this paper, we investigate the complex dynamical behaviors of a biological network that is derived from innate immune responses and that couples positive and negative feedback loops. The stability conditions of the non-negative equilibrium points (EPs) of the system are obtained, using the theory of dynamical systems, and we deduce that no more than three stable EPs exist in this system. Through bifurcation analysis and numerical simulations, we find that the system presents rich dynamical behaviors, such as monostability, bistability and oscillations. These results reveal how positive and negative feedback cooperatively regulate the dynamical behavior of the system.

scholarly journals Toll-Like Receptor (TLR) Signaling Enables Cyclic GMP-AMP Synthase (cGAS) Sensing of HIV-1 Infection in Macrophages

mBio ◽  
2021 ◽  
Author(s):  
Mohammad Adnan Siddiqui ◽  
Masahiro Yamashita
Keyword(s):  
Immune Responses ◽  
Cyclic Gmp ◽  
Immune Activation ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Tlr Signaling ◽  
Innate Immune Activation ◽  
Hiv 1

Innate immune activation is a hallmark of HIV-1 pathogenesis. Thus, it is critical to understand how HIV-1 infection elicits innate immune responses.

scholarly journals Subversion of Innate Immune Responses byBrucellathrough the Targeted Degradation of the TLR Signaling Adapter, MAL

2009 ◽  
Vol 184 (2) ◽  
pp. 956-964 ◽  
Author(s):  
Dola Sengupta ◽  
Alicia Koblansky ◽  
Jennifer Gaines ◽  
Tim Brown ◽  
A. Phillip West ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Tlr Signaling

scholarly journals TLR Signaling Tailors Innate Immune Responses in Human Microglia and Astrocytes

2005 ◽  
Vol 175 (7) ◽  
pp. 4320-4330 ◽  
Author(s):  
Carolyn S. Jack ◽  
Nathalie Arbour ◽  
Joshua Manusow ◽  
Vivianne Montgrain ◽  
Manon Blain ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Tlr Signaling ◽  
Human Microglia

scholarly journals The failure of B cells to induce non-canonical MYD88 splice variants correlates with lymphomagenesis via sustained NF-κB signaling

2020 ◽  
Author(s):  
Yamel Cardona Gloria ◽  
Stephan H. Bernhart ◽  
Sven Fillinger ◽  
Olaf-Oliver Wolz ◽  
Sabine Dickhöfer ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
B Cells ◽  
B Cell ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Splice Variants ◽  
Myeloid Cells ◽  
Negative Feedback Loop ◽  
Tlr Signaling ◽  
Splice Isoforms

AbstractGain-of-function mutations of the TLR adaptor and oncoprotein MyD88 drive B cell lymphomagenesis via sustained NF-κB activation. In myeloid cells, sustained TLR activation and NF-κB activation lead to the induction of inhibitory MYD88 splice variants that restrain prolonged NF-κB activation. We therefore sought to investigate whether such a negative feedback loop exists in B cells. Analyzing MYD88 splice variants in normal B cells and different primary B cell malignancies, we observed that MYD88 splice variants in transformed B cells are dominated by the canonical, strongly NF-κB-activating isoform of MYD88 and contain at least three novel, so far uncharacterized signaling-competent splice isoforms. TLR stimulation in B cells unexpectedly reinforces splicing of NF-κB-promoting, canonical isoforms rather than the ‘MyD88s’, a negative regulatory isoform that is typically induced by TLRs in myeloid cells. This suggests that an essential negative feedback loop restricting TLR signaling in myeloid cells at the level of alternative splicing, is missing in B cells, rendering B cells vulnerable to sustained NF-κB activation and eventual lymphomagenesis. Our results uncover MYD88 alternative splicing as an unappreciated promoter of B cell lymphomagenesis and provide a rationale why oncogenic MYD88 mutations are exclusively found in B cells.

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