scholarly journals Amino Acid‐Based Oral Rehydration Solution Mitigates Exertional Heat Stroke Severity but Does Not Alter the Innate Immune Response

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Michelle Ann King ◽  
Shauna Dineen ◽  
Jermaine Ward ◽  
Thomas Mayer ◽  
Mark Plamper ◽  
...  
Keyword(s):  
Immune Response ◽  
Amino Acid ◽  
Innate Immune Response ◽  
Oral Rehydration Solution ◽  
Heat Stroke ◽  
Innate Immune ◽  
Stroke Severity ◽  
Exertional Heat Stroke ◽  
Oral Rehydration ◽  
Rehydration Solution

An Amino Acid-Based Oral Rehydration Solution Increased Zinc Absorption in Irradiated Mice

2017 ◽  
Vol 152 (5) ◽  
pp. S812
Author(s):  
Reshu Gupta ◽  
Astrid Grosche ◽  
Xiaodong Xu ◽  
Liangjie Yin ◽  
Paul Okunieff ◽  
...  
Keyword(s):  
Amino Acid ◽  
Oral Rehydration Solution ◽  
Zinc Absorption ◽  
Oral Rehydration ◽  
Rehydration Solution

scholarly journals Comparison of Two Mice Strains, A/J and C57BL/6, in Caspase-1 Activity and IL-1βSecretion of Macrophage toMycobacterium lepraeInfection

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Tae Jin Kang ◽  
Geum Seon Lee ◽  
Se Kon Kim ◽  
Song Hou Jin ◽  
Gue Tae Chae
Keyword(s):  
Immune Response ◽  
Amino Acid ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Mycobacterium Leprae ◽  
Adaptor Proteins ◽  
Innate Immune ◽  
Intracellular Pathogens ◽  
Caspase 1 ◽  
Molecular Patterns

A/J mice were found to have amino acid differences in Naip5, one of the NOD-like receptors (NLRs) involved in the cytosolic recognition of pathogen-associated molecular patterns and one of the adaptor proteins for caspase-1 activation. This defect was associated with a susceptibility toLegionellainfection, suggesting an important role for Naip5 in the immune response also to other intracellular pathogens, such asMycobacterium leprae. In this study, the immune responses of macrophages from A/J mice againstM. lepraewere compared to those of macrophages from C57BL/6 mice. Infection withM. lepraeinduced high levels of TNF-αproduction and NF-κB activation in A/J and C57BL/6 macrophages. Caspase-1 activation and IL-1βsecretion were also induced in both macrophages. However, macrophages from A/J mice exhibited reduced caspase-1 activation and IL-1βsecretion compared to C57BL/6 macrophages. These results suggest that NLR family proteins may have a role in the innate immune response toM. leprae.

scholarly journals An Amino Acid–Based Oral Rehydration Solution Regulates Radiation-Induced Intestinal Barrier Disruption in Mice

2020 ◽  
Vol 150 (5) ◽  
pp. 1100-1108
Author(s):  
Reshu Gupta ◽  
Liangjie Yin ◽  
Astrid Grosche ◽  
Shanshan Lin ◽  
Xiaodong Xu ◽  
...  
Keyword(s):  
Amino Acid ◽  
Oral Rehydration Solution ◽  
Intestinal Barrier ◽  
Paracellular Permeability ◽  
Intestinal Barrier Function ◽  
Ultrastructural Changes ◽  
Oral Rehydration ◽  
Anion Selectivity ◽  
Radiation Induced ◽  
Rehydration Solution

ABSTRACT Background Radiotherapy inadvertently affects gastrointestinal (GI) epithelial cells, causing intestinal barrier disruption and increased permeability. Objective We examined the effect of amino acid–based oral rehydration solution (AA-ORS) on radiation-induced changes of intestinal barrier function and epithelial tight junctions (TJs) in a randomized experimental study using a total-body irradiation (TBI) mouse model. Methods Eight-week-old male Swiss mice received a single-dose TBI (0, 1, 3, or 5 Gy), and subsequent gastric gavage with AA-ORS (threonine, valine, serine, tyrosine, and aspartic acid) or saline for 2 or 6 d. Intestinal barrier function of mouse ileum was characterized by electrophysiological analysis of conductance, anion selectivity, and paracellular permeability [fluorescein isothiocyanate (FITC)-dextran]. Ultrastructural changes of TJs were evaluated by transmission electron microscopy. Membrane protein and mRNA expression of claudin-1, -2, -3, -5, and -7, occludin, and E-cadherin were analyzed with western blot, qPCR, and immunohistochemistry. Nonparametric tests were used to compare treatment-dose differences for each time point. Results Saline-treated mice had a higher conductance at doses as low as 3 Gy, and as early as 2 d post-TBI compared with 0 Gy (P < 0.001). Paracellular permeability and dilution potential were increased 6 d after 5 Gy TBI (P < 0.001). Conductance decreased with AA-ORS after 2 d in 3-Gy and 5-Gy mice (P < 0.05 and P < 0.001), and on day 6 after 5 Gy TBI (P < 0.001). Anion selectivity and FITC permeability decreased from 0.73 ± 0.02 to 0.61 ± 0.03 pCl/pNa (P < 0.01) and from 2.7 ± 0.1 × 105 to 2.1 ± 0.1 × 105 RFU (P < 0.001) in 5-Gy mice treated with AA-ORS for 6 d compared with saline. Irradiation-induced ultrastructural changes of TJs characterized by decreased electron density and gap formation improved with AA-ORS. Reduced claudin-1, -3, and -7 membrane expression after TBI recovered with AA-ORS within 6 d, whereas claudin-2 decreased indicating restitution of TJ proteins. Conclusions Radiation-induced functional and structural disruption of the intestinal barrier in mice is reversed by AA-ORS rendering AA-ORS a potential treatment option in prospective clinical trials in patients with gastrointestinal barrier dysfunction.

scholarly journals Murine Norovirus infection results in anti-inflammatory response downstream of amino acids depletion in macrophages

2021 ◽  
Author(s):  
Michèle Brocard ◽  
Jia Lu ◽  
Belinda Hall ◽  
Khushboo Borah ◽  
Carla Moller-Levet ◽  
...  
Keyword(s):  
Immune Response ◽  
Amino Acid ◽  
Stress Response ◽  
Viral Infection ◽  
Innate Immune Response ◽  
Metabolic Stress ◽  
Innate Immune ◽  
Murine Norovirus ◽  
Anti Inflammatory ◽  
Inflammatory Signalling

AbstractMurine norovirus (MNV) infection results in a late translation shut-off, that is proposed to contribute to the attenuated and delayed innate immune response observed both in vitro and in vivo. Recently, we further demonstrated the activation of the eIF2α kinase GCN2 during MNV infection, which has been previously linked to immunomodulation and resistance to inflammatory signalling during metabolic stress. While viral infection is usually associated with activation of dsRNA binding pattern recognition receptor PKR, we hypothesised that the establishment of a metabolic stress in infected cells is a proviral event, exploited by MNV to promote replication through weakening the activation of the innate immune response. In this study, we used multi-omics approaches to characterise cellular responses during MNV replication. We demonstrate the activation of pathways related to the integrated stress response, a known driver of anti-inflammatory phenotypes in macrophages. In particular, MNV infection causes an amino acid imbalance that is associated with GCN2 and ATF2 signalling. Importantly, this reprogramming lacks the features of a typical innate immune response, with the ATF/CHOP target GDF15 contributing to the lack of antiviral responses. We propose that MNV-induced metabolic stress supports the establishment of host tolerance to viral replication and propagation.ImportanceDuring viral infection, host defences are typically characterised by the secretion of pro-inflammatory autocrine and paracrine cytokines, potentiation of the IFN response and induction of the anti-viral response via activation of JAK and Stat signalling. To avoid these and propagate viruses have evolved strategies to evade or counteract host sensing. In this study, we demonstrate that murine norovirus controls the antiviral response by activating a metabolic stress response that activates the amino acid response and impairs inflammatory signalling. This highlights novel tools in the viral countermeasures tool-kit, and demonstrates the importance of the currently poorly understood metabolic reprogramming occurring during viral infections.

scholarly journals Whole-Genome Expression Profiling Reveals That Inhibition of Host Innate Immune Response Pathways by Ebola Virus Can Be Reversed by a Single Amino Acid Change in the VP35 Protein

2008 ◽  
Vol 82 (11) ◽  
pp. 5348-5358 ◽  
Author(s):  
Amy L. Hartman ◽  
Ling Ling ◽  
Stuart T. Nichol ◽  
Martin L. Hibberd
Keyword(s):  
Immune Response ◽  
Amino Acid ◽  
Host Cell ◽  
Innate Immune Response ◽  
Ebola Virus ◽  
Innate Immune ◽  
Single Amino Acid ◽  
Cell Responses ◽  
Single Amino Acid Change ◽  
Whole Genome Expression

ABSTRACT Ebola hemorrhagic fever is a rapidly progressing acute febrile illness characterized by high virus replication, severe immunosuppression, and case fatalities of ca. 80%. Inhibition of phosphorylation of interferon regulatory factor 3 (IRF-3) by the Ebola VP35 protein may block the host innate immune response and play an important role in the severity of disease. We used two precisely defined reverse genetics-generated Ebola viruses to investigate global host cell responses resulting from the inhibition of IRF-3 phosphorylation. The two viruses encoded either wild-type (WT) VP35 protein (recEbo-VP35/WT) or VP35 with an arginine (R)-to-alanine (A) amino acid substitution at position 312 (recEbo-VP35/R312A) within a previously defined IRF-3 inhibitory domain. When sucrose-gradient purified virus was used for infection, host cell whole-genome expression profiling revealed striking differences in human liver cell responses to these viruses differing by a single amino acid. The inhibition of host innate immune responses by WT Ebola virus was so potent that little difference in interferon and antiviral gene expression could be discerned between cells infected with purified WT, inactivated virus, or mock-infected cells. However, infection with recEbo-VP35/R312A virus resulted in a strong innate immune response including increased expression of MDA-5, RIG-I, RANTES, MCP-1, ISG-15, ISG-54, ISG-56, ISG-60, STAT1, IRF-9, OAS, and Mx1. The clear gene expression differences were obscured if unpurified virus stocks were used to initiate infection, presumably due to soluble factors present in virus-infected cell supernatant preparations. Ebola virus VP35 protein clearly plays a pivotal role in the potent inhibition of the host innate immune responses, and the present study indicates that VP35 has a wider effect on host cell responses than previously shown. The ability to eliminate this inhibitory effect with a single amino acid change in VP35 demonstrates the critical role this protein must play in the severe aspects this highly fatal disease.

scholarly journals Murine Norovirus infection results in anti-inflammatory response downstream of amino acid depletion in macrophages.

2021 ◽  
Author(s):  
Michèle Brocard ◽  
Jia Lu ◽  
Belinda Hall ◽  
Khushboo Borah ◽  
Carla Moller-Levet ◽  
...  
Keyword(s):  
Immune Response ◽  
Amino Acid ◽  
Stress Response ◽  
Viral Infection ◽  
Innate Immune Response ◽  
Metabolic Stress ◽  
Innate Immune ◽  
Murine Norovirus ◽  
Anti Inflammatory ◽  
Inflammatory Signalling

Murine norovirus (MNV) infection results in a late translation shut-off, that is proposed to contribute to the attenuated and delayed innate immune response observed both in vitro and in vivo. Recently, we further demonstrated the activation of the eIF2α kinase GCN2 during MNV infection, which has been previously linked to immunomodulation and resistance to inflammatory signalling during metabolic stress. While viral infection is usually associated with activation of dsRNA binding pattern recognition receptor PKR, we hypothesised that the establishment of a metabolic stress in infected cells is a proviral event, exploited by MNV to promote replication through weakening the activation of the innate immune response. In this study, we used multi-omics approaches to characterise cellular responses during MNV replication. We demonstrate the activation of pathways related to the integrated stress response, a known driver of anti-inflammatory phenotypes in macrophages. In particular, MNV infection causes an amino acid imbalance that is associated with GCN2 and ATF2 signalling. Importantly, this reprogramming lacks the features of a typical innate immune response, with the ATF/CHOP target GDF15 contributing to the lack of antiviral responses. We propose that MNV-induced metabolic stress supports the establishment of host tolerance to viral replication and propagation. Importance During viral infection, host defences are typically characterised by the secretion of pro-inflammatory autocrine and paracrine cytokines, potentiation of the IFN response and induction of the anti-viral response via activation of JAK and Stat signalling. To avoid these and propagate viruses have evolved strategies to evade or counteract host sensing. In this study, we demonstrate that murine norovirus controls the antiviral response by activating a metabolic stress response that activates the amino acid response and impairs inflammatory signalling. This highlights novel tools in the viral countermeasures arsenal, and demonstrates the importance of the currently poorly understood metabolic reprogramming occurring during viral infections.

Oral Immune Activation by Disgust and Disease-Related Pictures

2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Negative Control ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Markers ◽  
Before And After ◽  
Secondary Analyses ◽  
Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

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