Heterotypic Influenza Infections Mitigate Susceptibility to Secondary Bacterial Infection
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA849180 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Influenza associated bacterial super-infections have devastating impacts on the lung and can result in increased risk of mortality. New strains of influenza circulate throughout the population yearly promoting the establishment of immune memory. Nearly all individuals have some degree of influenza memory prior to adulthood. Due to this we sought to understand the role of immune memory during bacterial super-infections. An influenza heterotypic immunity model was established using influenza A/PR/8/34 and A/X31. We report here that influenza experienced mice are more resistant to secondary bacterial infection with methicillin-resistant Staphylococcus aureus as determined by wasting, bacterial burden, pulmonary inflammation, and lung leak, despite significant ongoing lung remodeling. Multidimensional flow cytometry and lung transcriptomics revealed significant alterations in the lung environment in influenza-experienced mice compared with naïve animals. These include changes in the lung monocyte and T cell compartments, characterized by increased expansion of influenza tetramer specific CD8+ T cells. The protection that was seen in memory experienced mouse model is associated with the reduction in inflammatory mechanisms making the lung less susceptible to damage and subsequent bacterial colonization. These findings provide insight into how influenza heterotypic immunity re-shapes the lung environment and the immune response to a re-challenge event, which is highly relevant to the context of human infection.
2022-06-27 | GSE206095 | GEO
Project description:Broadly protective antibodies against highly variable pathogens are very important for design of vaccines and therapeutics. We report that by administering two heterotypic influenza hemagglutinins (HAs) to mice by time difference, monoclonal antibodies can be obtained that bind strongly to both heterotypic influenza HAs. More interestingly, it was able to bind widely to the untreated subtype of HA.
2021-11-19 | GSE140720 | GEO
Project description:Males of many species, ranging from humans to insects, are more susceptible than females to parasitic, fungal, bacterial, and viral infections. One mechanism which has been proposed to account for this difference is the ‘immunocompetence handicap model’ which posits that the higher infectious disease burden in males is due to testosterone (T), which drives the development of secondary male sex characteristics at the expense of suppressing immunity. However, emerging data suggest that cell-intrinsic (chromosome X and Y) sex-specific factors may also contribute to the sex differences in infectious disease burden. Using a murine model of influenza A virus (IAV) infection and a panel of chromosome Y (ChrY) consomic strains on the C57BL/6J background, we present data showing that genetic variation in ChrY influences IAV pathogenesis in males. Specific ChrY variants increase susceptibility to IAV in males and augment pathogenic immune responses in the lung, including activation of pro-inflammatory IL-17-producing γδ T cells, without affecting viral replication. Additionally, susceptibility to IAV segregates independently of copy number variation (CNV) in multicopy ChrY gene families that influence susceptibility to other immunopathologic phenotypes, including survival following infection with Coxsackievirus B3. These results demonstrate a critical role for genetic variation in ChrY in regulating susceptibility to infectious disease.
2017-02-07 | GSE94540 | GEO
Project description:Immunization with two heterotypic influenza hemagglutinins by time difference effectively produces broadly binding antibodies against heterotypic influenza virus
| PRJNA590668 | ENA
Project description:Susceptibility to respiratory infections due to autosomal recessive IFIH1 mutations
| PRJNA351274 | ENA
Project description:Previous studies of our group have shown that IL-25 is essential for the resistance to E. caproni infections and the susceptibility of mice relies on the inability of this host species to produce IL-25 in response to infection (14-15). Susceptibility of mice to primary E. caproni infection was associated with low levels of intestinal IL-25 expression, whilst deworming via administration of praziquantel (pzq) was accompanied by a steady increase in IL-25 expression and, in turn, by the onset of a Th2-type response that prevented the establishment of secondary infections (14-15). Although these facts, little is known about the mechanism by which IL-25 generates resistance against intestinal helminths. In the present work, we analyze the changes in the production of proteins induced by IL-25 in the ileum of mice that may be involved in the generation of resistance against intestinal helminths.
2021-09-09 | PXD019477 | Pride
Project description:Global transcriptional responses in duodenal intestinal epithelia of chickens following primary and secondary Eimeria acervulina infections. Simple loop hybridization (day 0 vs. days 1-2, days 1-2 vs. 3-4, days 3-4 vs. 5-6, and days 5-6 vs. 7-8) per primary or secondary infections.
2010-05-18 | E-GEOD-16230 | biostudies-arrayexpress
Project description::Systemic duress, like that elicited by sepsis, burns or trauma, predispose patients to nosocomial pneumonia, demanding better understanding of host pathways influencing this deleterious connection. These pre-existing circumstances are capable of triggering the hepatic acute phase response (APR), which we previously demonstrated is essential for limiting susceptibility to secondary lung infections. To identify potential mechanisms underlying protection afforded by the lung-liver axis, our studies aimed to evaluate liver-dependent lung reprogramming when a systemic inflammatory challenge precedes pneumonia. WT mice and APR-deficient littermates lacking hepatocyte STAT3 (hepSTAT3-/-), a transcription factor necessary for full APR initiation, were challenged intraperitoneally with LPS to induce endotoxemia. After 18h, pneumonia was induced by intratracheal E. coli instillation. Endotoxemia elicited significant transcriptional alterations in the lungs of WT and hepSTAT3-/- mice, with nearly 2,000 differentially expressed genes between genotypes. The gene signatures revealed exaggerated immune activity in the lungs of hepSTAT3-/- mice, which were compromised in their capacity to launch additional cytokine responses to secondary infection. Proteomics revealed substantial liver-dependent modifications in the airspaces of pneumonic mice, implicating a network of dispatched liver-derived mediators influencing lung homeostasis. These results indicate that following systemic inflammation, liver acute phase changes dramatically remodel the lungs, resulting in a modified landscape for any stimuli encountered thereafter. Based on the established vulnerability of hepSTAT3-/- mice to secondary lung infections, we believe that intact liver function is critical for maintaining the immunological responsiveness of the lungs. Further studies are needed to confirm whether and how such lung changes directly influence pneumonia susceptibility.
2021-07-23 | PXD024663 | Pride
Project description:Nucleosomes that contain the histone variant H2A.Z are enriched around transcriptional start sites in many organisms. A single octameric nucleosome can contain two H2A.Z histones (homotypic) or one H2A.Z and one canonical H2A (heterotype). We generated high-resolution maps of homotypic and heterotypic Drosophila H2A.Z (H2Av) nucleosomes. Although homotypic and heterotypic H2Av nucleosomes map throughout most of the genome, homotypic nucleosomes are enriched and heterotypic nucleosomes are depleted downstream of active promoters and intron/exon boundaries. The distribution of homotypic H2A.Z nucleosomes resembles that of salt-soluble nucleosomes and shows evidence of displacement during transcriptional elongation. Homotypic nucleosomes are also depleted downstream of paused polymerases, where salt-soluble nucleosomes are conspicuously depleted. Our results suggest a model whereby H2A.Z enrichment patterns result from different structural interactions within the core of heterotypic and homotypic nucleosomes following disruption during transcriptional elongation. We analyzed two replicates for input, heterotypic and homotypic purifications. We sequenced one library for each of the single H2Av pulldown and 80mM salt soluble samples.
2010-11-01 | E-GEOD-21615 | biostudies-arrayexpress
Project description: Not available
| S-EPMC5481322 | biostudies-other