Adiponectin exacerbates influenza infection in elderly individuals via IL-18.
Ontology highlight
ABSTRACT:
SUBMITTER: Jiang Y
PROVIDER: S-EPMC7118100 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Publications
Adiponectin exacerbates influenza infection in elderly individuals via IL-18.
Jiang Youzhu Y Yi Changhua C Yi Yongxiang Y Jin Qingwen Q Kang Angray S AS Li Junwei J Kumar Sacitharan Pradeep P
Signal transduction and targeted therapy 20200403 1
Similar Datasets
Project description:Activators of innate immunity may have the potential to combat a broad range of infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent of adaptive immunity and interferon (IFN, type I and II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells elicited production of the cytokine interleukin-22 (IL-22), which induced a protective gene expression program in intestinal epithelial cells. Flagellin also induced NLRC4-dependent production of IL-18 and immediate elimination of RV-infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the capacity of flagellin to prevent or eliminate RV infection and thus holds promise as a broad-spectrum antiviral agent.
| S-EPMC4788408 | biostudies-literature
Project description:We previously reported adiponectin (AD) is highly expressed in the inflamed synovial joint tissue and correlates closely with progressive bone erosion in Rheumatoid arthritis (RA) patients. Here, we investigate the role of adiponectin in regulating Th17 response and the expression of receptor activator of nuclear factor-κB ligand (RANKL) in mice with CIA mice by intraarticularly injection of adiponectin into knee joints on day 17, day 20 and day 23 post first collagen immunization. The increased adiponectin expression was found in inflamed joint tissue of collagen-induced arthritis (CIA) mice. Adiponectin injection resulted in an earlier onset of arthritis, an aggravated arthritic progression, more severe synovial hyperplasia, bone erosion and osteoporosis in CIA mice. CD4(+)IL-17(+) Th17 cells, IL-17 mRNA and RANKL mRNA expression were markedly increased in the joint tissue of adiponectin treated CIA mice. Moreover, adiponectin treatment markedly enhanced Th17 cell generation from naive CD4(+) T cells in vitro, which accompanied by the high expression of Th17 transcription factor ROR-γt, and Th17 cytokine genes included IL-22 and IL-23. This study reveals a novel effect of adiponectin in exacerbating CIA progression by enhancing Th17 cell response and RANKL expression.
| S-EPMC4462752 | biostudies-literature
Project description:IntroductionFilipino Americans (FAs) are at high risk for developing type 2 diabetes despite other Asian phenotypes. Evidence suggests that pro-inflammatory interleukin-18 (IL-18) and anti-inflammatory adiponectin biomarkers associated with visceral adipose tissue (VAT) may explain this risk.ObjectivesThis study aimed to quantify the biomarkers in relation to standard ranges of VAT or typical circulating concentration ranges reported in the literature of IL-18 and adiponectin, examine relationships of these markers, and determine if they were different among those participants without diabetes, prediabetes, and diabetes.MethodsA cross-sectional study was used to enroll FAs without diabetes, prediabetes, or diabetes. VAT was measured using the InBody 570© Body Composition Analyzer. Blood samples were obtained to assess plasma concentrations of IL-18 and adiponectin using enzyme-linked immunosorbent assay. All analyses were conducted using a 5% type I error rate. Mean ±SD and percentages were used to describe the sample and data where appropriate. Pearson's correlations (R) were calculated to determine the relationships between VAT and IL-18 in each group. Analysis of variance was used to determine differences in VAT, IL-18, and adiponectin among groups. Further, nonparametric procedures examined the differences in adiponectin among those within groups.ResultsSeventy-five participants were enrolled. Biomarkers above the typical concentration range were observed for VAT, IL-18, and adiponectin. Adiponectin significantly differed among groups with lower values in the diabetes group vs. the nondiabetes group.ConclusionsThe findings indicate that while inflammation-related biomarkers, such as adiponectin, correlate with VAT and may serve as indicators of increased risk of type 2 diabetes in FAs, correlation alone does not establish causality.
| S-EPMC11320395 | biostudies-literature
Project description: Not available
| S-EPMC8298942 | biostudies-literature
Project description:Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infections. Understanding why some individuals get more serious disease may help with diagnosis and treatment. One possible risk factor underlying severe disease is bacterial exposure before RSV infection. Bacterial exposure has been associated with increased respiratory viral-induced disease severity but the mechanism remains unknown. Respiratory bacterial infections or exposure to their pathogen associated molecular patterns (PAMPs) trigger innate immune inflammation, characterised by neutrophil and inflammatory monocyte recruitment and the production of inflammatory cytokines. We hypothesise that these changes to the lung environment alter the immune response and disease severity during subsequent RSV infection. To test this, we intranasally exposed mice to LPS, LTA or Acinetobacter baumannii (an airway bacterial pathogen) before RSV infection and observed an early induction of disease, measured by weight loss, at days 1-3 after infection. Neutrophils or inflammatory monocytes were not responsible for driving this exacerbated weight loss. Instead, exacerbated disease was associated with increased IL-1α and TNF-α, which orchestrated the recruitment of innate immune cells into the lung. This study shows that exposure to bacterial PAMPs prior to RSV infection increases the expression of IL-1α and TNF-α, which dysregulate the immune response resulting in exacerbated disease.
| S-EPMC11631774 | biostudies-literature
Project description:Activators of innate immunity may have potential to combat a broad range of infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent of adaptive immunity and interferon (IFN, type I and II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells elicited production of the cytokine interleukin (IL)-22, which induced a protective gene expression program in intestinal epithelial cells. Flagellin also induced NLRC4-dependent production of IL-18 and immediate elimination of RV-infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the capacity of flagellin to prevent or eliminate RV infection, and thus holds promise as a broad-spectrum antiviral agent.
2014-11-30 | GSE62479 | GEO
Project description:Influenza virus targets epithelial cells in the upper respiratory tract. Natural Killer (NK) cell-mediated early innate defense responses to influenza infection include the killing of infected epithelial cells and generation of anti-viral cytokines including interferon gamma (IFN-γ). To date, it is unclear how the underlying cytokine milieu during infection regulates NK cell effector functions. Our data show during influenza infection myeloid cell-derived IL-27 regulates the early-phase effector functions of NK cells in the bronchioalveolar and lung tissue. Lack of IL-27R (Il27ra-/-) or IL-27 (Ebi3-/-) resulted in impaired NK cell effector functions including the generation of anti-viral IFN-γ responses. We identify CD27+CD11b+ NK cells as the primary subset that expresses IL-27R, which predominantly produces IFN-γ within the upper respiratory tract of the infected mice. IL-27 alone was incapable of altering the effector functions of NK cells. However, IL-27 sensitizes NK cells to augment both in vitro and in vivo responses mediated via the NKG2D receptor. This 'priming' function of IL-27 is mediated partly via transcriptional pathways regulated by Mafs and Nrf2 transcriptionally regulating TFAM and CPT1. Our data for the first time establishes a novel role for IL-27 in regulating early-phase effector functions of NK cells during influenza infection.
| S-EPMC6428861 | biostudies-literature
Project description:For more than a century, diabetic patients have been considered immunosuppressed due to defects in phagocytosis and microbial killing. We confirmed that diabetic mice were hypersusceptible to bacteremia caused by Gram-negative bacteria (GNB), dying at inocula nonlethal to nondiabetic mice. Contrary to the pervasive paradigm that diabetes impedes phagocytic function, the bacterial burden was no greater in diabetic mice despite excess mortality. However, diabetic mice did exhibit dramatically increased levels of proinflammatory cytokines in response to GNB infections, and immunosuppressing these cytokines with dexamethasone restored their resistance to infection, both of which are consistent with excess inflammation. Furthermore, disruption of the receptor for advanced glycation end products (RAGE), which is stimulated by heightened levels of AGEs in diabetic hosts, protected diabetic but not nondiabetic mice from GNB infection. Thus, rather than immunosuppression, diabetes drives lethal hyperinflammation in response to GNB by signaling through RAGE. As such, interventions to improve the outcomes from GNB infections should seek to suppress the immune response in diabetic hosts.IMPORTANCE Physicians and scientists have subscribed to the dogma that diabetes predisposes the host to worse outcomes from infections because it suppresses the immune system. This understanding was based largely on ex vivo studies of blood from patients and animals with diabetes. However, we have found that the opposite is true and worse outcomes from infection are caused by overstimulation of the immune system in response to bacteria. This overreaction occurs by simultaneous ligation of two host receptors: TLR4 and RAGE. Both signal via a common downstream messenger, MyD88, triggering hyperinflammation. In summary, contrary to hundred-year-old postulations about immune suppression in diabetic hosts, we find that diabetes instead predisposes to more severe infections because of additional inflammatory output through dual activation of MyD88 by not only TLR4 but also RAGE. It is the activation of RAGE during GNB infections in those with diabetes that accounts for their heightened susceptibility to infection compared to nondiabetic hosts.
| S-EPMC5565964 | biostudies-other
Project description:The influenza A virus (IAV) damages intestinal mucosal tissues beyond the respiratory tract. Probiotics play a crucial role in maintaining the balance and stability of the intestinal microecosystem. Extracellular vesicles (EVs) derived from probiotics have emerged as potential mediators of host immune response and anti-inflammatory effect. However, the specific anti-inflammatory effects and underlying mechanisms of probiotics-derived EVs on IAV remain unclear. In the present study, we investigated the therapeutic efficacy of Lactobacillus reuteri EHA2-derived EVs (LrEVs) in a mouse model of IAV infection. Oral LrEVs were distributed in the liver, lungs, and gastrointestinal tract. In mice infected with IAV, oral LrEVs administration alleviated IAV-induced damages in the lungs and intestines, modified the microbiota compositions, and increased the levels of short-chain fatty acids in those organs. Mechanistically, LrEVs exerted their protective effects against IAV infection by blunting the pro-inflammatory IL-17 signaling. Furthermore, FISH analysis detected miR-4239, one of the most abundant miRNAs in LrEVs, in both lung and intestinal tissues. We confirmed that miR-4239 directly targets IL-17a. Our findings paved the ground for future application of LrEVs in influenza treatment and offered new mechanistic insights regarding the anti-inflammatory role of miR-4239.
| S-EPMC11652895 | biostudies-literature
Project description:Salmonella Typhimurium (S.Tm) is a common cause of self-limiting diarrhea. The mucosal inflammation is thought to arise from a standoff between the pathogen's virulence factors and the host's mucosal innate immune defenses, particularly the mucosal NAIP/NLRC4 inflammasome. However, it had remained unclear how this switches the gut from homeostasis to inflammation. This was studied using the streptomycin mouse model. S.Tm infections in knockout mice, cytokine inhibition and -injection experiments revealed that caspase-1 (not -11) dependent IL-18 is pivotal for inducing acute inflammation. IL-18 boosted NK cell chemoattractants and enhanced the NK cells' migratory capacity, thus promoting mucosal accumulation of mature, activated NK cells. NK cell depletion and Prf-/- ablation (but not granulocyte-depletion or T-cell deficiency) delayed tissue inflammation. Our data suggest an NK cell perforin response as one limiting factor in mounting gut mucosal inflammation. Thus, IL-18-elicited NK cell perforin responses seem to be critical for coordinating mucosal inflammation during early infection, when S.Tm strongly relies on virulence factors detectable by the inflammasome. This may have broad relevance for mucosal defense against microbial pathogens.
| S-EPMC4920399 | biostudies-literature