DRAGONFLY KINGDOM NTERNATIONAL SERVICE AGENCY

Highlights

 Endogenous retrovirus sensing is required for commensal-

specific immunity

 Reverse transcription inhibition impairs commensal-induced

immunity in the skin

 cGAS/STING signaling in keratinocytes is required for skin

immunity to the microbiota

 Enhanced endogenous retrovirus expression promotes

microbiota-induced inflammation

Endogenous retroviruses promote homeostatic

and inflammatory responses to the microbiota

Djalma S. Lima-Junior,1,11 Siddharth R. Krishnamurthy,1,2,11 Nicolas Bouladoux,1,2 Nicholas Collins,1 Seong-Ji Han,1

Erin Y. Chen,3 Michael G. Constantinides,1,10 Verena M. Link,1,4 Ai Ing Lim,1 Michel Enamorado,1 Christophe Cataisson,5

Louis Gil,2 Indira Rao,1,6 Taylor K. Farley,1,7 Galina Koroleva,4 Jan Attig,8,9 Stuart H. Yuspa,5 Michael A. Fischbach,3

George Kassiotis,8,9 and Yasmine Belkaid1,2,12,*

1Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National

Institutes of Health, Bethesda, MD 20892, USA

2NIAID Microbiome Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA

3Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA 94305, USA

4NIH Center for Human Immunology, Bethesda, MD 20896, USA

5In Vitro Pathogenesis Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National

Institutes of Health, Bethesda, MD 20892, USA

6Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA

7Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of

Oxford, Roosevelt Drive, Oxford OX3 7FY, UK

8Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK

9Department of Medicine, Faculty of Medicine, Imperial College London, London W2 1PG, UK

10Present address: Department of Immunology and Microbiology, Scripps Research, La Jolla, CA 92037, USA

11These authors contributed equally

12Lead contact

*Correspondence: ybelkaid@niaid.nih.gov

https://doi.org/10.1016/j.cell.2021.05.020

SUMMARY

The microbiota plays a fundamental role in regulating host immunity. However, the processes involved in

the initiation and regulation of immunity to the microbiota remain largely unknown. Here, we show that the

skin microbiota promotes the discrete expression of defined endogenous retroviruses (ERVs). Keratino-

cyte-intrinsic responses to ERVs depended on cyclic GMP-AMP synthase (cGAS)/stimulator of interferon

genes protein (STING) signaling and promoted the induction of commensal-specific T cells. Inhibition of

ERV reverse transcription significantly impacted these responses, resulting in impaired immunity to the mi-

crobiota and its associated tissue repair function. Conversely, a lipid-enriched diet primed the skin for

heightened ERV- expression in response to commensal colonization, leading to increased immune re-

sponses and tissue inflammation. Together, our results support the idea that the host may have co-opted

its endogenous virome as a means to communicate with the exogenous microbiota, resulting in a multi-

kingdom dialog that controls both tissue homeostasis and inflammation..........

Abstract

Introduction SARS-CoV-2 vaccination is effective in preventing severe COVID-19, but efficacy in reducing viral load and transmission wanes over time. In addition, the emergence of novel SARS-CoV-2 variants increases the threat of uncontrolled dissemination and additional antiviral therapies are urgently needed for effective containment. In previous in vitro studies Echinacea purpurea demonstrated strong antiviral activity against enveloped viruses, including SARS-CoV-2. In this study, we examined the potential of Echinacea purpurea in preventing and treating respiratory tract infections (RTIs) and in particular, SARS-CoV-2 infections.

Methods 120 healthy volunteers (m,f, 18 – 75 years) were randomly assigned to Echinacea prevention or control group without any intervention. After a run-in week, participants went through 3 prevention cycles of 2, 2 and 1 months with daily 2’400mg Echinacea purpurea extract (Echinaforce®, EF). The prevention cycles were interrupted by breaks of 1 week. Acute respiratory symptoms were treated with 4’000 mg EF for up to 10 days, and their severity assessed via a diary. Naso/oropharyngeal swabs and venous blood samples were routinely collected every month and during acute illnesses for detection and identification of respiratory viruses, including SARS-CoV-2 via RT-qPCR and serology.

Results Summarized over all phases of prevention, 21 and 29 samples tested positive for any virus in the EF and control group, of which 5 and 14 samples tested SARS-CoV-2 positive (RR=0.37, Chi-square test, p=0.03). Overall, 10 and 14 symptomatic episodes occurred, of which 5 and 8 were COVID-19 (RR=0.70, Chi-square test, p>0.05). EF treatment when applied during acute episodes significantly reduced the overall virus load by at least 2.12 log10 or approx. 99% (t-test, p<0.05), the time to virus clearance by 8.0 days for all viruses (Wilcoxon test, p=0.02) and by 4.8 days for SARS-CoV-2 (p>0.05) in comparison to control. Finally, EF treatment significantly reduced fever days (1 day vs 11 days, Chi-square test, p=0.003) but not the overall symptom severity. There were fewer COVID-19 related hospitalizations in the EF treatment group (N=0 vs N=2).

Discussion/Conclusion EF exhibited antiviral effects and reduced the risk of viral RTIs, including SARS-CoV-2. By substantially reducing virus loads in infected subjects, EF offers a supportive addition to existing mandated treatments like vaccinations. Future confirmatory studies are warranted.

Indexed for CSH BMJ YALE  by Dragonfly Kingdom Library 

https://www.medrxiv.org/content/10.1101/2021.12.10.21267582v1

Abstract

Bats are a key reservoir of coronaviruses (CoVs), including the agent of the severe acute respiratory syndrome, SARS-CoV-2, responsible for the recent deadly viral pneumonia pandemic. However, understanding how bats can harbor several microorganisms without developing illnesses is still a matter under discussion. Viruses and other pathogens are often studied as stand-alone entities, despite that, in nature, they mostly live in multispecies associations called biofilms-both externally and within the host.

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Microorganisms in biofilms are enclosed by an extracellular matrix that confers protection and improves survival. Previous studies have shown that viruses can secondarily colonize preexisting biofilms, and viral biofilms have also been described. In this review, we raise the perspective that CoVs can persistently infect bats due to their association with biofilm structures. This phenomenon potentially provides an optimal environment for nonpathogenic and well-adapted viruses to interact with the host, as well as for viral recombination. Biofilms can also enhance virion viability in extracellular environments, such as on fomites and in aquatic sediments, allowing viral persistence and dissemination.

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Moreover, understanding the biofilm lifestyle of CoVs in reservoirs might contribute to explaining several burning questions as to persistence and transmissibility of highly pathogenic emerging CoVs.

Indexed for NIH Pubmed by Dragonfly Kingdom Library 

https://pubmed.ncbi.nlm.nih.gov/34190608/

available under aCC-BY-NC-ND 4.0 International license.

(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made

bioRxiv preprint doi: https://doi.org/10.1101/2021.10.29.466519; this version posted November 1, 2021.

Abstract

The majority of the population in South Africa use traditional health care to treat various mental conditions. In this review, we present ethnobotanical information on plants used by the traditional healers in South Africa to treat mental illnesses, specifically epilepsy, depression, age-related dementia and debilitative mental disorders. Details of the recent scientific studies conducted on some of these plants are reviewed. Extracts of Searsia chirindensis, Cotelydon orbiculata and Leonotis leonurus have shown in vivo anticonvulsant activity. Extracts from Searsia dentata and Searsia pyroides showed spontaneous epileptiform discharge in mouse cortical slices, and acted as NMDA-receptor antagonists. Apigenin, amentoflavone and agathisflavone with affinity to the benzodiazepine site on the GABA(A)-receptor were isolated from Searsia pyroides. Naringenin with affinity to the GABA(A)-benzodiazepine receptor was isolated from Mentha aquatica. Agapanthus campanulatus, Boophone disticha, Mondia whitei and Xysmalobium undulatum exhibited antidepressant-like activity in three in vivo models for depression. Amaryllidaceae alkaloids with activity to the serotonin transporter were isolated from Boophone disticha. The alkaloid mesembrine, which act as a serotonin reuptake inhibitor, was isolated from Sceletium tortuosum.

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Investigations of plants used to treat age-related dementia and debilitative mental disorders lead to the isolation of a number of Amaryllidaceae alkaloids with acetylcholinesterase inhibitory activity from Boophone disticha and Crinum species. Extracts of Mentha aquatica, Gasteria croucheri, Ruta graveolens and Scotia brachypetala inhibited MAO-B. Naringenin was isolated from Mentha aquatica as a MAO inhibitor. Only a small number of the more than 300 southern African plant species reported to treat or affect the CNS have been scientifically evaluated. Very few of the active compounds have been isolated and identified.

Agroecology is sustainable farming that works with nature.

Ecology is the study of relationships between plants, animals, people, and their environment - and the balance between these relationships.

Agroecology is the application of ecological concepts and principals in farming.

Agroecology promotes farming practices that;

Mitigate climate change - reducing emissions, recycling resources and prioritising local supply chains.

Work with wildlife - managing the impact of farming on wildlife and harnessing nature to do the hard work for us, such as pollinating crops and controlling pests.

Put farmers and communities in the driving seat - they give power to approaches led by local people and adapt agricultural techniques to suit the local area - and its specific social, environmental and economic conditions.

Agroecology in action

Agroforestry is a great example of agroecology. It's the practice of combining trees and farming; it demonstrates how food production and nature can co-exist.

Grazing farm animals under trees gives them shelter and fodder, whilst their manure enriches the soil. And planting trees on land normally used to grow cereal crops can provide another crop - be that fruit, nuts or timber. This provides another income stream for farmers and also protects soils from erosion, as the trees' deep roots help create a healthy soil structure.

Agroforestry, like many agroecological approaches, is a win-win.  ..........

Indexed for Soil Association by Dragonfly Kingdom Library

Abstract

Abstract

Although exposure to ultraviolet light is often viewed as pathogenic owing to its role in the genesis of skin cancer and skin aging, there is growing epidemiological evidence that such exposure may decrease risk for a number of more serious cancers, may have a favorable impact on blood pressure and vascular health, and may help to prevent certain autoimmune disorders - in addition to its well-known influence on bone density. Most likely, these health benefits are reflective of improved vitamin D status. Increased synthesis or intake of vitamin D can be expected to down-regulate parathyroid hormone (PTH), and to increase autocrine synthesis of its active metabolite calcitriol in certain tissues; these effects, in turn, may impact cancer risk, vascular health, immune regulation, and bone density through a variety of mechanisms. Presumably, a truly adequate supplemental intake of vitamin D - manyfold higher than the grossly inadequate current RDA - could replicate the benefits of optimal UV exposure, without however damaging the skin. Diets moderately low in bioavailable phosphate - like many vegan diets - might be expected to have a complementary impact on disease risks, inasmuch as serum phosphate suppresses renal calcitriol synthesis while up-regulating that of PTH. A proviso is that the impact of dietary phosphorus on bone health is more equivocal than that of vitamin D. Increased intakes of calcium, on the other hand, down-regulate the production of both PTH and calcitriol - the latter effect may explain why the impact of dietary calcium on cancer risk (excepting colon cancer), hypertension, and autoimmunity is not clearly positive. An overview suggests that a vegan diet supplemented with high-dose vitamin D should increase both systemic and autocrine calcitriol production while suppressing PTH secretion, and thus should represent a highly effective way to achieve the wide-ranging health protection conferred by optimal UV exposure.

Indexed for NIH Pubmed by Dragonfly Kingdom Library 

https://pubmed.ncbi.nlm.nih.gov/14592785/