Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA343118 | ENA |
REPOSITORIES: ENA
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Project description:Lung tissue-resident memory CD8+ T-cells (Trm) are critical for heterosubtypic immunity against influenza virus-(IAV)-reinfection. How these cells surveil the lung, respond to infection and interact with other cells remains unresolved. Here, we used mouse models to identify and enrich lung Trm in combination with intravital and static imaging to assess spatiotemporal dynamics of IAV-induced lung TRM before and after recall-infection. CD69+CD103+ Trm localize to sites of prior influenza infection where they exhibit substantially slower movement properties than non-Trm that also surveil the lung. After rechallenge, lung Trm form tight clusters in an antigen-dependent manner. IAV-specific Trm express several factors that regulate myeloid cell biology and their protective immune responses are accompanied by activation and migration of dendritic cells to draining lymph nodes and recruitment of inflammatory monocytes. Overall, these data reveal the dynamic landscapes of lung Trm cells associated with early protective immunity against IAV infection.
2024-07-22 | GSE242558 | GEO
Project description:Lung resident memory (Trm) CD8 T cells induced by influenza A virus (IAV), are pivotal for providing heterosubtypic immunity, but are not maintained long term, causing gradual loss of protection. This contrasts sharply with long-term maintenance of Trm induced by localized infections of the skin and other tissues. Here we show that the decline in lung Trm is determined by an imbalance between apoptosis and lung recruitment/conversion to Trm of circulating memory cells. At the cellular level, circulating effector memory (Tem) rather than central memory (Tcm) cells are the precursors for conversion to lung Trm. Time-dependent changes in expression of genes critical for Trm differentiation together with enrichment of Tcm diminish the capacity of circulating memory CD8 T cells to form Trm, explaining why IAV-induced Trm are not stably maintained over time. Importantly, systemic booster immunization, through increasing the number of circulating Tem cells, induces an increase in lung Trm pool, providing a new rational for future IAV vaccines.
2016-11-18 | GSE86973 | GEO
Project description:Resident memory T (TRM) cells in the lung are vital for heterologous protection against influenza A virus (IAV). Environmental factors are necessary to establish lung TRM, however the role of T cell intrinsic factors like T cell receptor (TCR) signal strength have not been elucidated. Here we investigated the impact of TCR signal strength on the generation and maintenance of lung TRM cells after IAV infection. We inserted high and low affinity OT-I epitopes into IAV and infected mice after transfer of OT-I T cells. We uncovered a bias in TRM formation in the lung elicited by lower affinity TCR stimulation. TCR affinity did not impact the overall phenotype or long-term maintenance of lung TRM cells. Overall, these findings demonstrate that TRM formation is negatively correlated with increased TCR signal strength. Lower affinity cells may have an advantage in forming TRM to ensure diversity in the antigen-specific repertoire in tissues.
2019-06-18 | GSE130609 | GEO
Project description:The importance of unanchored Ub in innate immunity has been shown only for a limited number of unanchored Ub-interactors. We investigated what additional cellular factors interact with unanchored Ub and whether unanchored Ub plays a broader role in innate immunity. To identify unanchored Ub-interacting factors from murine lungs, we used His-tagged recombinant poly-Ub chains as bait. These chains were mixed with lung tissue lysates and protein complexes were isolated with Ni-NTA beads. Sample elutions were subjected to mass spectrometry (LC-MSMS) analysis.
2022-02-28 | PXD031365 | Pride
Project description:Lung neutrophils are causally associated with IAV-induced disease severity. Less is known about the repertoire of lethal IAV-associated neutrophil proteins or about how global changes in different neutrophil compartments are coordinated following lethal IAV infection. Here, we use semi-quantitative proteomics to characterize dynamic alterations in BM, blood and lung neutrophils at homeostasis or following a lethal IAV infection, with a secondary aim of identifying lung neutrophil-derived proteins which are selectively induced following IAV infection. Our findings identify bone marrow neutrophil maturation as the key site of anti-viral activity induction, with further upregulation or release of both anti-viral and antimicrobial effectors occurring following lung tissue infiltration.
2019-05-29 | PXD012681 | Pride
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from Mus musculus tissues (Heart, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
2021-05-05 | PXD022309 | Pride
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from seven Mus musculus tissues (Heart, Brain, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
2018-04-24 | PXD007288 | Pride
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:An effective immune response to influenza A virus (IAV) requires two arms: host resistance, which restricts viral replication, and disease tolerance that limits tissue damage caused by the immune response to IAV. Interestingly, fatal influenza infections are more often associated with dysregulated inflammation, rather than an inability to control viral replication, highlighting the importance of mechanisms involved in disease tolerance to IAV. Here, we show that cyclophilin D (CypD), a mitochondrial protein known to regulate cell death and cytokine production, protects against IAV infection through disease tolerance. Mice deficient in CypD (CypD-/-) exhibit enhanced susceptibility to IAV infection, despite comparable myeloid immune responses and intact antiviral immunity. Instead, CypD-/- susceptibility was due to pulmonary tissue damage, caused by a lack of the cytokine IL-22 that protects the lung epithelium. We found the necessary source of IL-22 following IAV infection to be conventional natural killer (NK) cells that failed to reach the airways of infected CypD-deficient mice, as a result of dysregulated lymphopoiesis in the bone marrow. Importantly, following infection, a single administration of recombinant IL-22 in the airways abrogated pulmonary damage and rescued CypD-/- mice. Thus, the CypD/IL-22/NK cell axis is critical in immunity to IAV by promoting disease tolerance, limiting lung tissue damage and maintaining pulmonary function.
2022-06-21 | GSE163290 | GEO
Project description:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.
| S-EPMC11335981 | biostudies-literature