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:CD4 tissue-resident memory T cells (TRM) are crucial adaptive immune components involved in preventing influenza A virus (IAV) infection. Despite their importance, their physiological role in the upper respiratory tract, the first site of contact with IAV, remains unclear. Here, we find that, after IAV infection, antigen-specific CD4 TRM persist in the nasal tissue (NT) compartment after infection and provide protection upon heterosubtypic challenge. Single cell RNA sequencing analysis reveals that NT CD4 TRM are heterogeneous and transcriptionally distinct as compared to their lung counterparts. Mechanistically, we demonstrate that the CXCR6-CXCL16 axis promotes CD4 TRM residency in the NT. Furthermore, we show that the NT of mice and humans contains a high frequency of Th17 CD4 TRM that aid in local viral clearance and in reducing tissue damage. Collectively, our results support a robust physiological role for nasal tissue CD4 TRM in local protection during heterosubtypic IAV infection.
2026-02-26 | GSE270932 | 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:Immune responses in the lungs are essential for the prevention and control of a wide range of infections. Tissue-resident memory T (TRM) cells are critical for frontline immunity, yet in murine lungs they undergo rapid attrition, raising questions about their durability in the human lung. Here, using a T-cell receptor (TCR)-guided approach integrating single-cell transcriptomics with paired TCR repertoire profiling, we mapped over 87,000 pathogen-specific T cells from human lung tissue across 40 donors, many of whom harbored substantial TRM populations specific to multiple respiratory viruses. These findings suggest, contrary to observations in murine infection models, that the human lung is likely to serve as a reservoir of clonally expanded TRM cells specific to a broad spectrum of pathogens. Although the lung-associated lymph nodes (LLN) contained a small population of TRM cells, most TCRs from highly expanded TRM clones in the lungs were absent in the LLN, suggesting that LLNs are unlikely to serve as a major reservoir for lung TRM cells. While acquisition of the TRM phenotype in the lung was not biased towards specific pathogens, pathogen specificity influenced the transcriptional profiles of CD8+ TRM cells. Notably, influenza A virus (IAV)-specific CD8+ TRM cells expressed significantly higher levels of transcripts linked to tissue residence and effector properties compared to TRM cells specific to other pathogens. Overall, our findings reveal that the human lung retains a stable, yet diverse compartment of pathogen-specific TRM cells, with implications for understanding tissue-resident memory responses that persist after infections and vaccinations.
2026-06-07 | GSE305372 | GEO
Project description:Beyond a physical barrier, the lung epithelium provides an essential line of defense against infectious pathogens, such as Influenza A viruses (IAV), through antimicrobial factors and triggering innate and adaptive immunity. On the other hand, IAV infects lung epithelial cells and manipulates their function to establish a non-protective, permissive environment. Identification of epithelial factors and pathways that can be targeted to restore optimal immunity would provide new therapeutic options against IAV. Here, we demonstrate an unexpected non-immune function for the cytokine RELMɑ in mediating a permissive environment for IAV infection through lung epithelial cell-intrinsic effects. Murine infection with IAV A/California/04/2009 (H1N1) led to the significant RELMɑ secretion by IAV-infected EpCam+ epithelial cells. Both constitutive and club cell-specific RELMɑ-deficient mice (Retnla-/- and RetnlaΔCC10) had significantly reduced IAV virus, specifically in epithelial cells, whereas the lung immune response was unaffected. RELMɑ treatment increased IAV infection of murine lung epithelial cell lines (MLE), and transcriptomic analysis indicated that RELMɑ-induced permissiveness to IAV was associated with cell-intrinsic changes in metabolic activity. Collectively, these studies indicate a direct non-immune role for RELMɑ in mediating a virus-permissive environment in epithelial cells potentially through modulation of cellular metabolism.
2024-12-01 | GSE268747 | GEO
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