Estrogen Hormone Is an Essential Sex Factor Inhibiting Inflammation and Immune Response in COVID-19

Abstract Although vaccines have been evaluated and approved for SARS-CoV-2 infection prevention, there remains a lack of effective treatments to reduce the mortality of COVID-19 patients already infected with SARS-CoV-2. The global data of COVID-19 showed that men have a higher mortality rate than women. We further observed that the proportion of mortality of female increases starting from around the age of 55 significantly. Thus, sex is an essential factor associated with COVID-19 mortality, and sex related genetic factors could be interesting mechanisms and targets for COVID-19 treatment. However, the associated sex factors and signaling pathways remain unclear. Here, we propose to uncover the potential sex associated factors using systematic and integrative network analysis. The unique results indicated that estrogen hormones (ER), e.g., estrone and estriol, 1) interacting with ESR1/2 receptors, 2) can inhibit SARS-CoV-2 caused inflammation and immune response signaling in host cells; and 3) estrogen hormone is associated with the distinct fatality rates between male and female COVID-19 patients. Specifically, a high level of estradiol protecting young female COVID-19 patients, and estrogen loss to an extremely low level in females after about 55 years of age causing the increased fatality rate of women. In conclusion, estrogen hormone, interacting with ESR1/2 receptors, is an essential sex factor that protects COVID-19 patients by inhibiting inflammation and immune response caused by SARS-CoV-2 infection. Medications perturb the down-stream of ESR1/ESR2 to inhibit the inflammation and immune response can be effective or synergistic combined with other existing drugs for COVID-19 treatment.

Download Full-text

Coupled complementation of immune response genes controlling responsiveness to the H-2.2 alloantigen.

Journal of Experimental Medicine ◽

10.1084/jem.146.2.571 ◽

1977 ◽

Vol 146 (2) ◽

pp. 571-578 ◽

Cited By ~ 16

Author(s):

M E Dorf ◽

J H Stimpfling

Keyword(s):

Immune Response ◽

Immune Responses ◽

Humoral Response ◽

Mixed Lymphocyte Culture ◽

Lymphocyte Culture ◽

F1 Hybrids ◽

Gene Control ◽

Low Responder ◽

Resistant Strains ◽

High Level

The ability of various B10 congenic resistant strains to respond to the alloantigen H-2.2 was tested. High and low antibody-producing strains were distinguished by their anti-H-2.2 hemagglutinating respones. However, these strains do not differ in their ability to respond to these antigenic differences in the mixed lymphocyte culture. The humoral response to the H-2.2 alloantigen was shown to be controlled by two interacting genes localized within the H-2 complex. Thus, F1 hybrids prepared between parental low responder strains could yield high level immune responses. In addition, strains bearing recombinant H-2 haplotypes were used to map the two distinct genes controlling the immune response. The alleles at each locus were shown to be highly polymorphic as evidenced by the asymmetric complementation patterns observed. The restricted interactions of specific alleles was termed coupled complementation. The significance of the results in the terms of mechanisms of Ir gene control are discussed.

Download Full-text

Stromal hyaluronan accumulation is associated with low immune response and poor prognosis in pancreatic cancer

Scientific Reports ◽

10.1038/s41598-021-91796-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kyösti Tahkola ◽

Maarit Ahtiainen ◽

Jukka-Pekka Mecklin ◽

Ilmo Kellokumpu ◽

Johanna Laukkarinen ◽

...

Keyword(s):

Immune Response ◽

Immune Cell ◽

Geographical Area ◽

Prognostic Significance ◽

Staining Intensity ◽

Ductal Adenocarcinoma ◽

Poor Survival ◽

Negative Prognostic Factor ◽

High Level ◽

Immune Cell Score

AbstractHyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the prognostic significance of stromal HA accumulation and its association with host immune response in pancreatic ductal adenocarcinoma (PDAC). The study material consisted of 101 radically treated patients for PDAC from a single geographical area. HA staining was evaluated using a HA-specific probe, and the patterns of CD3, CD8, CD73 and PD-L1 expression were evaluated using immunohistochemistry. HA staining intensity of tumour stromal areas was assessed digitally using QuPath. CD3- and CD8-based immune cell score (ICS) was determined. High-level stromal HA expression was significantly associated with poor disease-specific survival (p = 0.037) and overall survival (p = 0.013) In multivariate analysis, high-level stromal HA expression was an independent negative prognostic factor together with histopathological grade, TNM stage, CD73 positivity in tumour cells and low ICS. Moreover, high-level stromal HA expression was associated with low ICS (p = 0.017). In conclusion, stromal HA accumulation is associated with poor survival and low immune response in PDAC.

Download Full-text

Bacterial Cyclic Dinucleotides and the cGAS–cGAMP–STING Pathway: A Role in Periodontitis?

Pathogens ◽

10.3390/pathogens10060675 ◽

2021 ◽

Vol 10 (6) ◽

pp. 675

Author(s):

Samira Elmanfi ◽

Mustafa Yilmaz ◽

Wilson W. S. Ong ◽

Kofi S. Yeboah ◽

Herman O. Sintim ◽

...

Keyword(s):

Immune Response ◽

Periodontal Disease ◽

Innate Immune ◽

Host Cells ◽

Type I Interferons ◽

Type I ◽

Vaccine Adjuvants ◽

Cyclic Dinucleotides ◽

Sting Pathway

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides—including c-di-GMP, c-di-AMP, and cGAMP—of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to the production of Type I interferons and proinflammatory cytokines. In this review, we (1) focus on the possible role of bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway in the pathogenesis of periodontal disease and the regulation of periodontal immune response, and (2) review and discuss activators and inhibitors of the STING pathway as immune response regulators and their potential utility in the treatment of periodontitis. PubMed/Medline, Scopus, and Web of Science were searched with the terms “STING”, “TBK 1”, “IRF3”, and “cGAS”—alone, or together with “periodontitis”. Current studies produced evidence for using STING-pathway-targeting molecules as part of anticancer therapy, and as vaccine adjuvants against microbial infections; however, the role of the STING/TBK1/IRF3 pathway in periodontal disease pathogenesis is still undiscovered. Understanding the stimulation of the innate immune response by cyclic dinucleotides opens a new approach to host modulation therapies in periodontology.

Download Full-text

Bioinformatics Analysis of Allele Frequencies and Expression Patterns of ACE2, TMPRSS2 and FURIN in Different Populations and Susceptibility to SARS-CoV-2

Genes ◽

10.3390/genes12071041 ◽

2021 ◽

Vol 12 (7) ◽

pp. 1041

Author(s):

Mohammad Tarek ◽

Hana Abdelzaher ◽

Firas Kobeissy ◽

Hassan A. N. El-Fawal ◽

Mohammed M. Salama ◽

...

Keyword(s):

Immune Response ◽

Genetic Factors ◽

Bioinformatics Analysis ◽

Expression Patterns ◽

Spike Protein ◽

Target Cells ◽

Health Crisis ◽

Expression Levels ◽

Different Populations ◽

Shed Light

The virus responsible for the COVID-19 global health crisis, SARS-CoV-2, has been shown to utilize the ACE2 protein as an entry point to its target cells. The virus has been shown to rely on the actions of TMPRSS2 (a serine protease), as well as FURIN (a peptidase), for the critical priming of its spike protein. It has been postulated that variations in the sequence and expression of SARS-CoV-2’s receptor (ACE2) and the two priming proteases (TMPRSS2 and FURIN) may be critical in contributing to SARS-CoV-2 infectivity. This study aims to examine the different expression levels of FURIN in various tissues and age ranges in light of ACE2 and TMPRSS2 expression levels using the LungMAP database. Furthermore, we retrieved expression quantitative trait loci (eQTLs) of the three genes and their annotation. We analyzed the frequency of the retrieved variants in data from various populations and compared it to the Egyptian population. We highlight FURIN’s potential interplay with the immune response to SARS-CoV-2 and showcase a myriad of variants of the three genes that are differentially expressed across populations. Our findings provide insights into potential genetic factors that impact SARS-CoV-2 infectivity in different populations and shed light on the varying expression patterns of FURIN.

Download Full-text

Still’s Disease in the Constellation of Hyperinflammatory Syndromes: A Link with Kawasaki Disease?

Journal of Clinical Medicine ◽

10.3390/jcm10153244 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3244

Author(s):

Perrine Dusser ◽

Isabelle Koné-Paut

Keyword(s):

Immune Response ◽

Kawasaki Disease ◽

Innate Immune Response ◽

Adaptive Response ◽

Genetic Factors ◽

Innate Immune ◽

Cytokine Storm ◽

Still’S Disease ◽

Still's Disease ◽

Excessive Activation

Still’s disease and Kawasaki disease (KD) today belong to the group of cytokine storm syndromes, a pathophysiological set related to excessive activation of the innate immune response. We present here a personal vision of what can link these two diseases, taking up their concepts at their beginning. By their many clinical and physiopathological similarities, we conclude that they constitute a common spectrum whose fate is modified by subtle differences in terms of adaptive response that could, in part, be driven by genetic factors.

Download Full-text

High level expression of the Drosophila Toll receptor ectodomain and crystallization of its complex with the morphogen Spätzle

Biological Chemistry ◽

10.1515/hsz-2013-0136 ◽

2013 ◽

Vol 394 (8) ◽

pp. 1091-1096 ◽

Cited By ~ 2

Author(s):

Marco Stelter ◽

Uwe Fandrich ◽

Kati Franzke ◽

Angelika Schierhorn ◽

Constanze Breithaupt ◽

...

Keyword(s):

Immune Response ◽

High Level Expression ◽

Receptor Ligand ◽

High Affinity ◽

Cystine Knot ◽

Toll Receptor ◽

Cystine Knot Protein ◽

High Yields ◽

High Level ◽

Affinity Interaction

Abstract Drosophila Toll receptors are involved in embryonic development and in the immune response of adult flies. In both processes, the Toll receptor ligand is the NGF-like cystine knot protein Spätzle. Here we present the expression of Toll receptor ectodomain in Schneider cells at high yields and demonstrate a high affinity interaction with the refolded and trypsin-processed Spätzle cystine knot domain dimer. Poorly and anisotropically diffracting crystals of the complex could be improved by deglycosylation and dehydration, paving the way for structural analyses of the Toll-Spätzle interaction.

Download Full-text

Mycobacterium tuberculosis adhesins: potential biomarkers as anti-tuberculosis therapeutic and diagnostic targets

Microbiology ◽

10.1099/mic.0.082206-0 ◽

2014 ◽

Vol 160 (9) ◽

pp. 1821-1831 ◽

Cited By ~ 22

Author(s):

Viveshree S. Govender ◽

Saiyur Ramsugit ◽

Manormoney Pillay

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

Control Strategies ◽

Host Cells ◽

Tuberculosis Control ◽

Surface Molecules ◽

Host Pathogen Interaction ◽

Bacterial Aggregation ◽

Insight Into

Adhesion to host cells is a precursor to host colonization and evasion of the host immune response. Conversely, it triggers the induction of the immune response, a process vital to the host’s defence against infection. Adhesins are microbial cell surface molecules or structures that mediate the attachment of the microbe to host cells and thus the host–pathogen interaction. They also play a crucial role in bacterial aggregation and biofilm formation. In this review, we discuss the role of adhesins in the pathogenesis of the aetiological agent of tuberculosis, Mycobacterium tuberculosis. We also provide insight into the structure and characteristics of some of the characterized and putative M. tuberculosis adhesins. Finally, we examine the potential of adhesins as targets for the development of tuberculosis control strategies.

Download Full-text

Heavy metal intoxication compromises the host cytokine response in Ascaris Suum model infection

Helminthologia ◽

10.1515/helmin-2015-0063 ◽

2016 ◽

Vol 53 (1) ◽

pp. 14-23 ◽

Cited By ~ 2

Author(s):

E. Dvorožňáková ◽

M. Dvorožňáková ◽

J. Šoltys

Keyword(s):

Heavy Metal ◽

Immune Response ◽

Ascaris Suum ◽

Cytokine Response ◽

Parasitic Infections ◽

Tnf Α ◽

Ifn Γ ◽

High Level ◽

Larval Burden ◽

Heavy Metal Intoxication

SummaryLead (Pb), Cadmium (Cd) and Mercury (Hg) are recognized for their deleterious effect on the environment and immunity where subsequently compromised immune response affects the susceptibility to the potential parasitic infections. This study examined the host cytokine response after heavy metal intoxication (Pb, Cd, and Hg) and subsequent Ascaris suum infection in BALB/c mice. Pb modulated murine immune response towards the Th2 type of response (delineated by IL-5 and IL-10 cytokine production) what was also dominant for the outcome of A. suum infection. Chronic intoxication with Pb caused a more intensive development of the parasite infection. Cd stimulated the Th1 immune response what was associated with increase in IFN-γ production and reduction of larvae present in the liver of intoxicated mice. The larval burden was also low in mice intoxicated with Hg. This was probably not related to the biased Th1/Th2 type of immune response, but rather to the bad host conditions caused by mercury toxicity and high level of pro-cachectic cytokine TNF-α.

Download Full-text

Molecular biology of baculovirus and its use in biological control in Brazil

Pesquisa Agropecuária Brasileira ◽

10.1590/s0100-204x1999001000001 ◽

1999 ◽

Vol 34 (10) ◽

pp. 1733-1761 ◽

Cited By ~ 4

Author(s):

Maria Elita Batista de Castro ◽

Marlinda Lobo de Souza ◽

William Sihler ◽

Júlio Carlyle Macedo Rodrigues ◽

Bergmann Morais Ribeiro

Keyword(s):

Molecular Biology ◽

Recombinant Dna ◽

Host Cells ◽

Virus Propagation ◽

Viral Particles ◽

Occlusion Bodies ◽

Budded Virus ◽

Recombinant Dna Techniques ◽

High Level ◽

Eukaryotic Organisms

Baculoviruses are insect viruses found mainly in Lepidoptera. The family Baculoviridae is taxonomically divided in two genera, Nucleopolyhedrovirus and Granulovirus, which differ by occlusion body morphology. NPVs (Nucleopolyhedroviruses) have polyhedrical inclusion bodies (PIBs) containing multiple viral particles, while GVs (Granuloviruses) appear to be generally single particles occluded in oval shaped occlusion bodies. During the life cycle, two different viral progenies are produced: BV (Budded Virus) and PDV (Polyhedra Derived Virus), which are essential for the infectious process and virus propagation in host cells. Baculoviruses are being used for pest control and they are especially safe due to their specificity and invertebrate-restricted host range. Baculoviruses have been used as vectors for high level protein expression ofheterologous genes from prokaryotic and eukaryotic organisms. Also, recombinant DNA techniques have allowed the production of genetically modified viral insecticides. This study is a review on the taxonomy, structure, replication and molecular biology of baculoviruses, as well as their use as bioinsecticides in Brazil.

Download Full-text

Tumour viruses and innate immunity

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2016.0267 ◽

2017 ◽

Vol 372 (1732) ◽

pp. 20160267 ◽

Cited By ~ 13

Author(s):

Sharon E. Hopcraft ◽

Blossom Damania

Keyword(s):

Immune Response ◽

Inflammatory Response ◽

Viral Infection ◽

Innate Immune Response ◽

Innate Immune ◽

Host Cells ◽

Oncogenic Viruses ◽

Barr Virus ◽

Human T Cell ◽

Epstein Barr

Host cells sense viral infection through pattern recognition receptors (PRRs), which detect pathogen-associated molecular patterns (PAMPs) and stimulate an innate immune response. PRRs are localized to several different cellular compartments and are stimulated by viral proteins and nucleic acids. PRR activation initiates signal transduction events that ultimately result in an inflammatory response. Human tumour viruses, which include Kaposi's sarcoma-associated herpesvirus, Epstein–Barr virus, human papillomavirus, hepatitis C virus, hepatitis B virus, human T-cell lymphotropic virus type 1 and Merkel cell polyomavirus, are detected by several different PRRs. These viruses engage in a variety of mechanisms to evade the innate immune response, including downregulating PRRs, inhibiting PRR signalling, and disrupting the activation of transcription factors critical for mediating the inflammatory response, among others. This review will describe tumour virus PAMPs and the PRRs responsible for detecting viral infection, PRR signalling pathways, and the mechanisms by which tumour viruses evade the host innate immune system. This article is part of the themed issue ‘Human oncogenic viruses’.

Download Full-text