Mycobacterium tuberculosis infection drives a Type I IFN signature in lung lymphocytes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA825579 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18725036_1.fastq.gz | Fastqsanger.gz | |||
| SRR18725036_2.fastq.gz | Fastqsanger.gz | |||
| SRR18725037_1.fastq.gz | Fastqsanger.gz | |||
| SRR18725037_2.fastq.gz | Fastqsanger.gz | |||
| SRR18725038_1.fastq.gz | Fastqsanger.gz |
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Project description:Mycobacterium tuberculosis (Mtb) infects a quarter of the world’s population and causes tuberculosis (TB), which is a leading cause of death globally. A clear understanding of the dynamics of immune response at cellular level is crucial to design better strategies to control TB. We have employed single-cell RNA-seq approach on lung lymphocytes derived from healthy and Mtb-infected mice. Our results show enrichment of type I IFN responsive phenotypes among the lymphoid cell clusters, as well as heat shock responses in natural killer (NK) cells from Mtb-infected mice lungs. We have identified Ly6A as a novel lymphoid cell activation marker and validated its upregulation in activated lymphoid cells post Mtb infection. The cross analysis of type I IFN signature in human TB infected peripheral blood samples further validates our results. These findings significantly contribute toward understanding and characterizing the transcriptional parameters at single-cell depth in a highly relevant and reproducible mouse model of TB.
2022-06-24 | GSE200639 | GEO
Project description:Cutaneous leishmaniasis is a localized infection controlled by CD4+ T cells that produce IFN-g within lesions. Phagocytic cells recruited to lesions, such as monocytes, are then exposed to IFN-g which triggers their ability to kill the intracellular parasites. Consistent with this, a transcriptional analysis of lesions from patients identified the presence of a strong interferon stimulated gene (ISG) signature. To determine what systemic responses are occurring that might influence the disease, we performed RNA sequencing (RNA-seq) on the blood of L. braziliensis-infected patients, as well as healthy controls. Functional enrichment analysis identified a transcriptional ISG signature as the dominant response in the blood of patients. An increase in monocytes and macrophages in the blood, estimated from our RNA-seq dataset, was positively correlated with this ISG signature. Consistent with this result, patients had circulating IFN-g in their serum. A cytotoxicity signature, which is a dominant feature in the lesions, was also found in the blood and correlated with an increased abundance of cytolytic cells. Thus, two transcriptional signatures present in lesions were found systemically, although with a substantially reduced number of differentially expressed genes (DEGs). Finally, we found that the number of DEGs and ISGs in leishmaniasis was similar to tuberculosis – another localized infection – but significantly less than observed in malaria. In contrast, the cytolytic signature and increased cytolytic cell abundance was not found in tuberculosis or malaria. Our results indicate that systemic signatures can reflect what is occurring in leishmanial lesions. Furthermore, the presence of an ISG signature in blood monocytes and macrophages suggests that when these cells enter lesions they may already be primed to control the parasites.
2021-03-23 | GSE162760 | GEO
Project description:Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-g signature
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Project description:The critical role of type I IFN (IFN I ) in viral disease is thoroughly documented while their function in bacterial infection remains ambiguous. General interest in biological functions of IFN I in Mycobacterium tuberculosis (Mtb) infection was raised by the identification of a distinct IFN I gene expression signature in tuberculosis (TB) patients. Here we demonstrate that TB-susceptible mice lacking the receptor for IFN I (IFNAR1) were protected from death upon aerogenic infection with Mtb. Increased survival was accompanied by reduced bacterial burden and ameliorated lung pathology as well as diminished production of proinflammatory IL-1?, among other cytokines. IFNAR1 signaling did not affect T cell responses, but markedly altered migration of inflammatory monocytes and neutrophils to the lung during pulmonary TB. This process was orchestrated by presence of IFNAR1 in both immune and tissue-resident radioresistant cells. IFNAR1-driven TB susceptibility was initiated by CXCL5/CXCL1-driven accumulation of neutrophils into alveoli and subsequently a distinct compartmentalization of Mtb in lung phagocytes. We conclude that IFN I alters early innate events at the site of Mtb invasion leading to unleashed inflammation. Hence, our data furnish a mechanistic explanation for the detrimental role of IFN I in pulmonary TB. dual-color color-swap
2013-12-31 | E-GEOD-44848 | biostudies-arrayexpress
Project description:Mycobacterium tuberculosis (Mtb) infects 25% of the world's population and causes tuberculosis (TB), which is a leading cause of death globally. A clear understanding of the dynamics of immune response at the cellular level is crucial to design better strategies to control TB. We use the single-cell RNA sequencing approach on lung lymphocytes derived from healthy and Mtb-infected mice. Our results show the enrichment of the type I IFN signature among the lymphoid cell clusters, as well as heat shock responses in natural killer (NK) cells from Mtb-infected mice lungs. We identify Ly6A as a lymphoid cell activation marker and validate its upregulation in activated lymphoid cells following infection. The cross-analysis of the type I IFN signature in human TB-infected peripheral blood samples further validates our results. These findings contribute toward understanding and characterizing the transcriptional parameters at a single-cell depth in a highly relevant and reproducible mouse model of TB.
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Project description:The critical role of type I IFN (IFN I ) in viral disease is thoroughly documented while their function in bacterial infection remains ambiguous. General interest in biological functions of IFN I in Mycobacterium tuberculosis (Mtb) infection was raised by the identification of a distinct IFN I gene expression signature in tuberculosis (TB) patients. Here we demonstrate that TB-susceptible mice lacking the receptor for IFN I (IFNAR1) were protected from death upon aerogenic infection with Mtb. Increased survival was accompanied by reduced bacterial burden and ameliorated lung pathology as well as diminished production of proinflammatory IL-1?, among other cytokines. IFNAR1 signaling did not affect T cell responses, but markedly altered migration of inflammatory monocytes and neutrophils to the lung during pulmonary TB. This process was orchestrated by presence of IFNAR1 in both immune and tissue-resident radioresistant cells. IFNAR1-driven TB susceptibility was initiated by CXCL5/CXCL1-driven accumulation of neutrophils into alveoli and subsequently a distinct compartmentalization of Mtb in lung phagocytes. We conclude that IFN I alters early innate events at the site of Mtb invasion leading to unleashed inflammation. Hence, our data furnish a mechanistic explanation for the detrimental role of IFN I in pulmonary TB.
2013-12-31 | GSE44848 | GEO
Project description:The source of IFN-γ in ovarian cancer microenvironment and its biological effect to the tumor cells is unclear. The immortalized human ovarian surface epithelial cell line, HOSE-E7/hTERT (HOSE) was treated with IFN-γ and expression microarray analysis was performed, and probes showing significantly higher values in IFN-γ-added group were termed â??IFN-γ signature genes (295 probes)â??. We then applied this signature to our ovarian cancer microarray data, which included 75 ovarian cancer clinical samples, by means of ss-GSEA. IFN-γ signature score was strongly correlated to the number of infiltrating CD4-positive or CD8-positive lymphocytes in the tumors. These data suggest that the IFN-γ in the ovarian cancer microenvironment is derived from lymphocytes, and an IFN-γ-rich microenvironment is strongly correlated to a lymphocyte-rich microenvironment. HOSE cells were incubated in 8 separate culture dishes, 4 dishes with and 4 dishes without 500 IU/ml recombinant human IFN-γ (R&D Systems) in the culture medium for 6 hours prior to the analysis.
2014-03-04 | E-GEOD-55510 | biostudies-arrayexpress
Project description:The source of IFN-γ in ovarian cancer microenvironment and its biological effect to the tumor cells is unclear. The immortalized human ovarian surface epithelial cell line, HOSE-E7/hTERT (HOSE) was treated with IFN-γ and expression microarray analysis was performed, and probes showing significantly higher values in IFN-γ-added group were termed “IFN-γ signature genes (295 probes)”. We then applied this signature to our ovarian cancer microarray data, which included 75 ovarian cancer clinical samples, by means of ss-GSEA. IFN-γ signature score was strongly correlated to the number of infiltrating CD4-positive or CD8-positive lymphocytes in the tumors. These data suggest that the IFN-γ in the ovarian cancer microenvironment is derived from lymphocytes, and an IFN-γ-rich microenvironment is strongly correlated to a lymphocyte-rich microenvironment.
2014-03-04 | GSE55510 | GEO
Project description:IFN-α-producing proliferating myeloid cells reveal type I IFN-stimulating gene signature
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Project description:We previously established a method to generate myeloid lineage cells with proliferation capacity from induced pluripotent stem cells (iPSCs) (Zhang R. Cancer Immunol Res. 3: 668, 2015). In this study, we generated the IFN-α-producing cells by genetic engineering of mouse iPSC-derived myeloid cells (iPSC-pMCs). Gene expression profiling of IFN-α-producing iPSC-pMCs (IFN-α-iPSC-pMCs) revealed a distinct interferon-stimulated gene (ISG) signature: of 613 differentially expressed genes (versus iPSC-pMC), 345 genes were ISGs of which > 70 % were type I IFN-related. Gene ontology analysis showed that the up-regulated gene signature was enriched for transcripts associate with immune responses, cellular responses to type I IFN, and defense responses to virus.
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