Crosstalk among Jasmonate, Salicylate and Ethylene Signaling Pathways in Plant Disease and Immune Responses

Abstract The use of direct-acting antivirals (DAAs) therapy for the treatment of hepatitis C virus (HCV) results in a high sustained virological response (SVR) and subsequently alters liver immunologic environment. However, hepatocellular carcinoma (HCC) may occur after DAAs treatment. We aimed to clarify changes of immune responses, PI3K/AKT and JAK/STAT signaling pathways in HCV-induced liver diseases and HCC following DAAs treatment. Four cohorts are classified as chronic HCV patients, HCV-related cirrhosis without HCC, HCV-related cirrhosis and HCC, and healthy control group. The patient groups were further divided into treated or untreated with DAAs with SVR12. Increased percentages of CD3, CD8 and CD4, decreased CD4/FoxP3/CD25, CD8/PD-1 and CD19/PDL-1 were found in DAAs-treated patients in the three HCV groups. Following DAAs therapy, the levels of ROS, IL-1β, IL-6, IL-8 and TNF-α were significantly decreased in the three HCV groups. Treated HCV patients showed up regulation of p-AKT and p-STAT5 and down regulation of p-STAT3, HIF-1α and COX-2. In conclusion, DAAs enhance the immune response in chronic HCV and liver cirrhosis, hence our study is the first to show change in PI3K/AKT and JAK/STAT signaling pathways in different HCV-induced liver diseases after DAAs. In chronic HCV, DAAs have better impact on the immune response while in liver cirrhosis not all immune changes were prominent.

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Lipopolysaccharide activates innate immune responses in murine intestinal myofibroblasts through multiple signaling pathways

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00022.2008 ◽

2009 ◽

Vol 296 (3) ◽

pp. G601-G611 ◽

Cited By ~ 65

Author(s):

Kristen L. W. Walton ◽

Lisa Holt ◽

R. Balfour Sartor

Keyword(s):

Immune Responses ◽

Signaling Pathways ◽

P38 Mapk ◽

Western Blotting ◽

Pi3 Kinase ◽

Innate Immune ◽

Innate Immune Responses ◽

Fold Induction ◽

Cox 2 ◽

Multiple Signaling

Myofibroblasts (MF) play an important role in intestinal wound healing. A compromised epithelial barrier exposes intestinal subepithelial MF to luminal bacterial products. However, responses of murine intestinal MF to bacterial adjuvants and potential roles of intestinal MF in innate immune responses are not well defined. Our aims in this study were to determine innate immune responses and intracellular signaling pathways of intestinal MF exposed to LPS, a prototypic Toll-like receptor (TLR) ligand. Expression of TLR4 in primary murine intestinal MF cultures was confirmed by RT-PCR and Western blotting. LPS-induced secretion of prostaglandin E2 (PGE2), interleukin (IL)-6, and keratinocyte-derived chemokines (KC) was measured by ELISA. Intracellular responses to LPS were assessed by Western blotting for NF-κB p65, Iκ-Bα, Akt, p38 MAP kinase, and cyclooxygenase-2 (COX-2). LPS induced rapid phosphorylation of NF-κB p65, Akt, and p38 MAPK and degradation of Iκ-Bα. LPS induced expression of COX-2 and secretion of PGE2 (2.0 ± 0.8-fold induction vs. unstimulated cells), IL-6 (6.6 ± 0.4-fold induction), and KC (12.5 ± 0.4-fold induction). Inhibition of phosphoinositide-3 (PI3)-kinase, p38 MAPK, or NF-κB pathways reduced LPS-induced PGE2, IL-6, and KC secretion. These studies show that primary murine intestinal MF respond to LPS, evidenced by activation of NF-κB, PI3-kinase, and MAPK signaling pathways and secretion of proinflammatory molecules. Inhibition of these pathways attenuated LPS-dependent PGE2, IL-6, and KC production, indicating that LPS activates MF by multiple signaling pathways. These data support the hypothesis that MF are a component of the innate immune system and may exert paracrine effects on adjacent epithelial and immune cells by responding to luminal bacterial adjuvants.

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Herpes Simplex Virus 1 Infection of Neuronal and Non-Neuronal Cells Elicits Specific Innate Immune Responses and Immune Evasion Mechanisms

Frontiers in Immunology ◽

10.3389/fimmu.2021.644664 ◽

2021 ◽

Vol 12 ◽

Author(s):

Amanda L. Verzosa ◽

Lea A. McGeever ◽

Shun-Je Bhark ◽

Tracie Delgado ◽

Nicole Salazar ◽

...

Keyword(s):

Herpes Simplex ◽

Epithelial Cells ◽

Immune Responses ◽

Host Cell ◽

Signaling Pathways ◽

Sensory Neurons ◽

Immune Evasion ◽

Innate Immune ◽

Innate Immune Responses ◽

Hsv 1

Alphaherpesviruses (α-HV) are a large family of double-stranded DNA viruses which cause many human and animal diseases. There are three human α-HVs: Herpes Simplex Viruses (HSV-1 and HSV-2) and Varicella Zoster Virus (VZV). All α-HV have evolved multiple strategies to suppress or exploit host cell innate immune signaling pathways to aid in their infections. All α-HVs initially infect epithelial cells (primary site of infection), and later spread to infect innervating sensory neurons. As with all herpesviruses, α-HVs have both a lytic (productive) and latent (dormant) stage of infection. During the lytic stage, the virus rapidly replicates in epithelial cells before it is cleared by the immune system. In contrast, latent infection in host neurons is a life-long infection. Upon infection of mucosal epithelial cells, herpesviruses immediately employ a variety of cellular mechanisms to evade host detection during active replication. Next, infectious viral progeny bud from infected cells and fuse to neuronal axonal terminals. Here, the nucleocapsid is transported via sensory neuron axons to the ganglion cell body, where latency is established until viral reactivation. This review will primarily focus on how HSV-1 induces various innate immune responses, including host cell recognition of viral constituents by pattern-recognition receptors (PRRs), induction of IFN-mediated immune responses involving toll-like receptor (TLR) signaling pathways, and cyclic GMP‐AMP synthase stimulator of interferon genes (cGAS-STING). This review focuses on these pathways along with other mechanisms including autophagy and the complement system. We will summarize and discuss recent evidence which has revealed how HSV-1 is able to manipulate and evade host antiviral innate immune responses both in neuronal (sensory neurons of the trigeminal ganglia) and non-neuronal (epithelial) cells. Understanding the innate immune response mechanisms triggered by HSV-1 infection, and the mechanisms of innate immune evasion, will impact the development of future therapeutic treatments.

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A patatin-like protein synergistically regulated by jasmonate and ethylene signaling pathways plays a negative role in Nicotiana attenuata resistance to Alternaria alternata

Plant Diversity ◽

10.1016/j.pld.2018.12.001 ◽

2019 ◽

Vol 41 (1) ◽

pp. 7-12 ◽

Cited By ~ 2

Author(s):

Junbin Cheng ◽

Na Song ◽

Jinsong Wu

Keyword(s):

Signaling Pathways ◽

Alternaria Alternata ◽

Nicotiana Attenuata ◽

Ethylene Signaling ◽

Negative Role

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Signaling Pathways Activated by HIV and Their Impact on Immune Responses

RNA Viruses ◽

10.1142/9789812833808_0002 ◽

2009 ◽

pp. 31-58

Author(s):

Katrina Gee ◽

Sasmita Mishra ◽

Wei Ma ◽

Marko Kryworuchko ◽

Ashok Kumar

Keyword(s):

Immune Responses ◽

Signaling Pathways

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Immunologic Consequences of Hypoxia during Critical Illness

Anesthesiology ◽

10.1097/aln.0000000000001163 ◽

2016 ◽

Vol 125 (1) ◽

pp. 237-249 ◽

Cited By ~ 10

Author(s):

Harmke D. Kiers ◽

Gert-Jan Scheffer ◽

Johannes G. van der Hoeven ◽

Holger K. Eltzschig ◽

Peter Pickkers ◽

...

Keyword(s):

Immune Responses ◽

Signaling Pathways ◽

Daily Practice ◽

Innate Immune ◽

Protective Effects ◽

Innate Immune Responses ◽

Downstream Signaling ◽

Pathogen Clearance ◽

Pharmacologic Modulation ◽

Oxygen Status

Abstract Hypoxia and immunity are highly intertwined at clinical, cellular, and molecular levels. The prevention of tissue hypoxia and modulation of systemic inflammation are cornerstones of daily practice in the intensive care unit. Potentially, immunologic effects of hypoxia may contribute to outcome and represent possible therapeutic targets. Hypoxia and activation of downstream signaling pathways result in enhanced innate immune responses, aimed to augment pathogen clearance. On the other hand, hypoxia also exerts antiinflammatory and tissue-protective effects in lymphocytes and other tissues. Although human data on the net immunologic effects of hypoxia and pharmacologic modulation of downstream pathways are limited, preclinical data support the concept of tailoring the immune response through modulation of the oxygen status or pharmacologic modulation of hypoxia-signaling pathways in critically ill patients.

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Bacillus subtilis and Pseudomonas fluorescens Trigger Common and Distinct Systemic Immune Responses in Arabidopsis thaliana Depending on the Pathogen Lifestyle

Vaccines ◽

10.3390/vaccines8030503 ◽

2020 ◽

Vol 8 (3) ◽

pp. 503

Author(s):

Ngoc Huu Nguyen ◽

Patricia Trotel-Aziz ◽

Sandra Villaume ◽

Fanja Rabenoelina ◽

Adrian Schwarzenberg ◽

...

Keyword(s):

Bacillus Subtilis ◽

Immune Responses ◽

Signaling Pathways ◽

Pseudomonas Syringae ◽

Systemic Resistance ◽

Functional Study ◽

Marker Genes ◽

Beneficial Bacteria ◽

Bacillus Spp ◽

Immune Pathways

Plants harbor various beneficial bacteria that modulate their innate immunity, resulting in induced systemic resistance (ISR) against various pathogens. However, the immune mechanisms underlying ISR triggered by Bacillus spp. and Pseudomonas spp. against pathogens with different lifestyles are not yet clearly elucidated. Here, we show that root drenching of Arabidopsis plants with Pseudomonas fluorescensPTA-CT2 and Bacillus subtilis PTA-271 can induce ISR against the necrotrophic fungus B. cinerea and the hemibiotrophic bacterium Pseudomonas syringae Pst DC3000. In the absence of pathogen infection, both beneficial bacteria do not induce any consistent change in systemic immune responses. However, ISR relies on priming faster and robust expression of marker genes for the salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) signaling pathways upon pathogen challenge. These responses are also associated with increased levels of SA, JA, and abscisic acid (ABA) in the leaves of bacterized plants after infection. The functional study also points at priming of the JA/ET and NPR1-dependent defenses as prioritized immune pathways in ISR induced by both beneficial bacteria against B. cinerea. However, B. subtilis-triggered ISR against Pst DC3000 is dependent on SA, JA/ET, and NPR1 pathways, whereas P. fluorescens-induced ISR requires JA/ET and NPR1 signaling pathways. The use of ABA-insensitive mutants also pointed out the crucial role of ABA signaling, but not ABA concentration, along with JA/ET signaling in primed systemic immunity by beneficial bacteria against Pst DC3000, but not against B. cinerea. These results clearly indicate that ISR is linked to priming plants for enhanced common and distinct immune pathways depending on the beneficial strain and the pathogen lifestyle.

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The Effect of Adenosine on TLR Signaling Pathways in Human Monocytic THP-1 Cells.

Blood ◽

10.1182/blood.v104.11.3828.3828 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3828-3828

Author(s):

Chin-Fu Chen ◽

Chun-Huai Cheng ◽

Seychelle Vos

Keyword(s):

Immune Responses ◽

Signaling Pathways ◽

Immune Cells ◽

Adenosine Receptors ◽

Protein Modification ◽

Map Kinases ◽

Critical Role ◽

Innate Immune ◽

Fcγ Receptors ◽

Tlr Signaling

Abstract Adenosine is an important metabolite that serves as a potent regulator of inflammation and mediates various biological functions in different cell types. Adenosine inhibits the proinflammatory actions of inflammatory and immune cells via interaction with its receptors, particularly A2A receptors. Adenosine receptors belong to the seven-transmembrane G-protein coupled receptors and via the different G proteins transfer signals through different effectors including adenyl cyclase, PKA, PKC, PI3K, and MAP kinases. The mechanisms by which the adenosine regulates immune responses and how adenosine receptor pathways interact with other signaling pathways are currently unknown. Toll-like receptors (TLRs) of the innate immune cells recognize conserved microbial structures, such as bacterial lipopolysaccharide and viral double-stranded RNA, and activate signaling pathways that result in innate immune responses against microbial infections. Fcγ receptors of the innate cells play a critical role in the clearance of pathogens, regulation of inflammation and co-ordination of the immune response. We seek to understand the interaction between adenosine (via adenosine receptors) and TLR- and Fcγ R- mediated signaling pathways. We have initiated study on the effect of adenosine and lipopolysaccharide (LPS) on expression of TLR2, TLR4, FcγRI and Fcγ RII receptors in the human monocytic cell line THP-1. We incubated cells with 100μM adenosine for three hours at 37°C and assayed the expression of receptors using flow cytometry. Our results suggest that adenosine increases the expression of TLR2 and TLR4 in both undifferentiated cells and the cells induced to become macrophages by phorbol ester. Incubation with adenosine for 24 hours further increases the expression of TLR2 and TLR4 in both undifferentiated and differentiated THP-1 cells. Similarly, incubation with LPS for three hours increases the expression TLR2 and TLR4 in both undifferentiated and differentiated THP-1 cells. In contrast, the expression level of FcγRI and FcγRII receptors do not change in the presence of either adenosine or LPS. These observations suggest that adenosine specifically enhances expression of TLRs but not Fcγ receptors. To further understand the interaction between adenosine and TLR pathways, we are continuously investigating the effect of adenosine on expression and the protein modification (e.g. phosphorylation) of TLR2, TLR4, and the molecules in the TLR signaling cascades including MyD88, IRAK and MAP kinases using real-time RT-PCR and western blotting.

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