scholarly journals Natural Mucosal Barriers and COVID-19 in Children

2021 ◽  
Author(s):  
Carl A. Pierce ◽  
Sharlene Sy ◽  
Benjamin Galen ◽  
Doctor Y Goldstein ◽  
Erika Orner ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Outcomes ◽  
Severe Disease ◽  
Mucosal Immune Response ◽  
Innate Immune ◽  
Interferon Signaling ◽  
Expression Of Genes ◽  
Gene And Protein Expression ◽  
Ifn Γ ◽  
Nasal Fluid

AbstractCOVID-19 is more benign in children compared to adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesized that a more robust early innate immune response to SARS-CoV-2 may protect against severe disease and compared clinical outcomes, viral copies and cellular gene and protein expression in nasopharyngeal swabs from 12 children and 27 adults upon presentation to the Emergency Department. SARS-CoV-2 copies were similar, but compared to adults, children displayed higher expression of genes associated with interferon signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-α2, IFN-γ, IP-10, IL-8, and IL-1β protein were detected in nasal fluid in children versus adults. Anti-SARS-CoV-2 IgA and IgG were detected in nasal fluid from both groups and correlated negatively with mucosal IL-18. These findings suggest that a vigorous mucosal immune response in children compared to adults contributes to favorable clinical outcomes.

scholarly journals DNA Methylation Patterns of Interferon Gamma Gene Promoter and Serum Level in Pulmonary Tuberculosis: Their Role in Prognosis

2019 ◽  
Vol 16 (1) ◽  
pp. 0178
Author(s):  
Zayr Et al.
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Interferon Gamma ◽  
Gene Promoter ◽  
Innate Immune ◽  
Healthy Controls ◽  
Healthy Control ◽  
Ifn Γ ◽  
Methylation Patterns ◽  
Normal Controls

Tuberculosis (TB) still remains an important medical problem due to high levels of morbidity and mortality worldwide. A series of innate immune mechanisms that create a cytokine network control the pathogenesis of tuberculosis and this response has the capacity to modify the host genomic DNA structure through epigenetic mechanisms such as DNA methylation which could constantly alter the local gene expression pattern that can modulate the metabolism of the tissues and the immune-response. Interferon-gamma (IFN-γ) is an important pro-inflammatory cytokine regulator of the innate immune response to TB. This study aims to determine DNA methylation patterns of INF-γ gene promoter and measure serum IFN- γ level in newly diagnosed TB patients, relapse TB patients, and healthy control, in order to study the possibility of using these as a biomarker for the prognosis of TB stages in patients. The current case-control study included 66 patients with TB and 33 healthy control subjects. DNA was extracted from peripheral blood(PB) of included subjects and modified using sodium bisulfate specific kit. DNA methylation patterns of IFN-γ gene promoter was determine by using methylation specific polymerase chain reaction(MS-PCR).Serum IFN-γ level  was determined using enzyme linked immune-sorbent assay(ELISA). Results showed that percentages of DNA methylation patterns in normal controls, newly diagnostic TB patients and relapse TB patients were (63.3%, 18.2% and 21.2% respectively). Also, higher significant differences (P≤0.0001) of  un-methylated  IFN-γ gene promoter patterns in newly diagnostic TB patients  than  relapse TB patients comparison with healthy controls. The percentage of un-methylated DNA patterns in healthy controls, newly diagnostic TB patients and relapse TB patients were (9.9%, 39.4% and 51.5%, respectively). The mean of serum IFN-γ levels (pg/ml) for normal controls, newly diagnostic TB patients and relapse TB patients were (59.3± 13.8,75.8±24.3 and 69.6±18.7,respectively).In conclusion, there is a relative association between methylation of IFN-γ gene promoter and predisposing to TB progression.

scholarly journals The Exopolysaccharide of Lactobacillus fermentum UCO-979C Is Partially Involved in Its Immunomodulatory Effect and Its Ability to Improve the Resistance against Helicobacter pylori Infection

2020 ◽  
Vol 8 (4) ◽  
pp. 479
Author(s):  
Valeria Garcia-Castillo ◽  
Guillermo Marcial ◽  
Leonardo Albarracín ◽  
Mikado Tomokiyo ◽  
Patricia Clua ◽  
...  
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Helicobacter Pylori Infection ◽  
Beneficial Effects ◽  
Ifn Γ ◽  
H Pylori

Lactobacillus fermentum UCO-979C (Lf979C) beneficially modulates the cytokine response of gastric epithelial cells and macrophages after Helicobacter pylori infection in vitro. Nevertheless, no in vivo studies were performed with this strain to confirm its beneficial immunomodulatory effects. This work evaluated whether Lf979C improves protection against H. pylori infection in mice by modulating the innate immune response. In addition, we evaluated whether its exopolysaccharide (EPS) was involved in its beneficial effects. Lf979C significantly reduced TNF-α, IL-8, and MCP-1 and augmented IFN-γ and IL-10 in the gastric mucosa of H. pylori-infected mice. The differential cytokine profile induced by Lf979C in H. pylori-infected mice correlated with an improved reduction in the pathogen gastric colonization and protection against inflammatory damage. The purified EPS of Lf979C reduced IL-8 and enhanced IL-10 levels in the gastric mucosa of infected mice, while no effect was observed for IFN-γ. This work demonstrates for the first time the in vivo ability of Lf979C to increase resistance against H. pylori infection by modulating the gastric innate immune response. In addition, we advanced knowledge of the mechanisms involved in the beneficial effects of Lf979C by demonstrating that its EPS is partially responsible for its immunomodulatory effect.

The Innate Immune Response, Clinical Outcomes, and Ex Vivo HCV Antiviral Efficacy of a TLR7 Agonist (PF-4878691)

2011 ◽  
Vol 89 (6) ◽  
pp. 821-829 ◽  
Author(s):  
M D Fidock ◽  
B E Souberbielle ◽  
C Laxton ◽  
J Rawal ◽  
O Delpuech-Adams ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Outcomes ◽  
Innate Immune Response ◽  
Ex Vivo ◽  
Innate Immune ◽  
Antiviral Efficacy ◽  
Tlr7 Agonist

scholarly journals Innate Immune Responses of Bat and Human Cells to Filoviruses: Commonalities and Distinctions

2017 ◽  
Vol 91 (8) ◽  
Author(s):  
Ivan V. Kuzmin ◽  
Toni M. Schwarz ◽  
Philipp A. Ilinykh ◽  
Ingo Jordan ◽  
Thomas G. Ksiazek ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Antiviral Effect ◽  
Human Cells ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Symptomatic Disease ◽  
Ifn Γ

ABSTRACT Marburg (MARV) and Ebola (EBOV) viruses are zoonotic pathogens that cause severe hemorrhagic fever in humans. The natural reservoir of MARV is the Egyptian rousette bat (Rousettus aegyptiacus); that of EBOV is unknown but believed to be another bat species. The Egyptian rousette develops subclinical productive infection with MARV but is refractory to EBOV. Interaction of filoviruses with hosts is greatly affected by the viral interferon (IFN)-inhibiting domains (IID). Our study was aimed at characterization of innate immune responses to filoviruses and the role of filovirus IID in bat and human cells. The study demonstrated that EBOV and MARV replicate to similar levels in all tested cell lines, indicating that permissiveness for EBOV at cell and organism levels do not necessarily correlate. Filoviruses, particularly MARV, induced a potent innate immune response in rousette cells, which was generally stronger than that in human cells. Both EBOV VP35 and VP24 IID were found to suppress the innate immune response in rousette cells, but only VP35 IID appeared to promote virus replication. Along with IFN-α and IFN-β, IFN-γ was demonstrated to control filovirus infection in bat cells but not in human cells, suggesting host species specificity of the antiviral effect. The antiviral effects of bat IFNs appeared not to correlate with induction of IFN-stimulated genes 54 and 56, which were detected in human cells ectopically expressing bat IFN-α and IFN-β. As bat IFN-γ induced the type I IFN pathway, its antiviral effect is likely to be partially induced via cross talk. IMPORTANCE Bats serve as reservoirs for multiple emerging viruses, including filoviruses, henipaviruses, lyssaviruses, and zoonotic coronaviruses. Although there is no evidence for symptomatic disease caused by either Marburg or Ebola viruses in bats, spillover of these viruses into human populations causes deadly outbreaks. The reason for the lack of symptomatic disease in bats infected with filoviruses remains unknown. The outcome of a virus-host interaction depends on the ability of the host immune system to suppress viral replication and the ability of a virus to counteract the host defenses. Our study is a comparative analysis of the host innate immune response to either MARV or EBOV infection in bat and human cells and the role of viral interferon-inhibiting domains in the host innate immune responses. The data are useful for understanding the interactions of filoviruses with natural and accidental hosts and for identification of factors that influence filovirus evolution.

scholarly journals Tristetraprolin prevents gastric metaplasia in mice by suppressing pathogenic inflammation

2021 ◽  
Author(s):  
Jonathan T. Busada ◽  
Stuti Kadka ◽  
Kylie N. Peterson ◽  
Deborah J. Stumpo ◽  
Lecong Zhou ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Immune Activation ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Innate Immune ◽  
Cancer Development ◽  
Expression Of Genes ◽  
Gastric Metaplasia ◽  
Spasmolytic Polypeptide

AbstractAberrant immune activation is associated with numerous inflammatory and autoimmune diseases and contributes to cancer development and progression. Within the stomach, inflammation drives a well-established sequence from gastritis to metaplasia, eventually resulting in adenocarcinoma. Unfortunately, the processes that regulate gastric inflammation and prevent carcinogenesis remain unknown. Tristetraprolin (TTP) is an RNA-binding protein that promotes the turnover of numerous pro-inflammatory and oncogenic mRNAs. Here, we utilized a TTP-overexpressing model, the TTPΔARE mouse, to examine whether TTP can protect the stomach from adrenalectomy (ADX)-induced gastric inflammation and spasmolytic polypeptide-expressing metaplasia (SPEM). We found that TTPΔARE mice were completely protected from ADX-induced gastric inflammation and SPEM. RNA sequencing revealed that TTP overexpression suppressed the expression of genes associated with the innate immune response. Finally, we show that protection from gastric inflammation was only partially due to suppression of Tnf, a well-known TTP target. Our results demonstrate that TTP exerts broad anti-inflammatory effects in the stomach and suggest that therapies that increase TTP expression may be effective treatments of pro-neoplastic gastric inflammation.

scholarly journals How Many Mammalian Reovirus Proteins are involved in the Control of the Interferon Response?

Pathogens ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 83 ◽  
Author(s):  
Delphine Lanoie ◽  
Simon Boudreault ◽  
Martin Bisaillon ◽  
Guy Lemay
Keyword(s):  
Immune Response ◽  
Host Cell ◽  
Innate Immune Response ◽  
Resistance Mechanisms ◽  
Innate Immune ◽  
Interferon Response ◽  
Gene Products ◽  
Interferon Signaling ◽  
Host Cell Response ◽  
Response Network

As with most viruses, mammalian reovirus can be recognized and attacked by the host-cell interferon response network. Similarly, many viruses have developed resistance mechanisms to counteract the host-cell response at different points of this response. Reflecting the complexity of the interferon signaling pathways as well as the resulting antiviral response, viruses can—and often have—evolved many determinants to interfere with this innate immune response and allow viral replication. In the last few years, it has been evidenced that mammalian reovirus encodes many different determinants that are involved in regulating the induction of the interferon response or in interfering with the action of interferon-stimulated gene products. In this brief review, we present our current understanding of the different reovirus proteins known to be involved, introduce their postulated modes of action, and raise current questions that may lead to further investigations.

scholarly journals Induction of an Embryonic Mouse Innate Immune Response following Inoculation In Utero with Minute Virus of Mice

2014 ◽  
Vol 89 (4) ◽  
pp. 2182-2191 ◽  
Author(s):  
Irina Rostovsky ◽  
Claytus Davis
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
In Utero ◽  
Innate Immune ◽  
Productive Infection ◽  
Interferon Response ◽  
Minute Virus Of Mice ◽  
Embryonic Mouse ◽  
Minute Virus ◽  
Ifn Γ

ABSTRACTWe used an embryonic-infection model system to show that MVMp, the prototypic minute virus of mice (MVM) serotype and a member of the genusProtoparvovirus, triggers a comprehensive innate immune response in the developing mouse embryo. Direct inoculation of the midtrimester embryoin uterowith MVMp results in a widespread, productive infection. During a 96-h infection course, embryonic beta interferon (IFN-β) and IFN-γ transcription were induced 90- and 60-fold, respectively. IFN-β levels correlated with the embryo viral burden, while IFN-γ levels first increased and then decreased. Production of proinflammatory cytokines, interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α), also increased, but by smaller amounts, approximately 7-fold each. We observed increased levels of downstream antiviral effector molecules, PKR and phosphorylated STAT2. Finally, we showed that there is an immune cell response to the virus infection. Infected tissues in the embryo exhibited an increased density of mature leukocytes compared to the same tissues in uninfected embryos. The responses we observed were almost completely restricted to the infected embryos. Uninfected littermates routinely exhibited small increases in innate immune components that rarely reached statistical significance compared to negative controls. Similarly, the placentae of infected embryos did not show any significant increase in transcription of innate immune cytokines. Since the placenta has both embryonic and maternal components, we suggest there is minimal involvement of the dam in the response to infection.IMPORTANCEInteraction between the small single-stranded vertebrate DNA viruses, the protoparvoviruses, and the host innate immune system has been unclear. The issue is important practically given the potential use of these viruses as oncotherapeutic agents. The data reported here stand in contrast to studies of innate immune response during protoparvovirus infection of adult hosts, which invariably reported no or minimal and sporadic induction of an interferon response during infection. We conclude that under conditions of robust and productive MVM infection, a normal murine host is able to mount a significant and broad innate immune response.

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