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ABSTRACT:
PROVIDER: PRJNA1086664 | ENA |
REPOSITORIES: ENA
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Project description:Pneumocystis pneumonia is an opportunistic pneumonia that has been increasing in non-HIV patients in recent years. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis, we profile the transcriptomes of mouse lungs with Pneumocystis pneumonia and from uninfected control subjects using single-cell RNA sequencing, yielding multiple populations of myeloid cells, T cells and B cells. We uncover a PCP-associated TREM2+ subpopulation of interstitial macrophages, which expands in PCP, differentiates from Ly6C+ monocytes. We also define the subsets of effector CD4+ T cells that expand after the infection of Pneumocystis. Finally, intercellular crosstalk between interstitial macrophages and effector CD4+ T cells via multiple ligand and receptor interactions reveals several anti-pneumocystis pathways. Our work dissects unanticipated aspects of the cellular and molecular basis of Pneumocystis pneumonia at a single-cell level, and provides a conceptual framework for the discovery of rational therapeutic targets in Pneumocystis pneumonia.
2021-03-26 | GSE157627 | GEO
Project description:Pneumocystis pneumonia is the most common serious opportunistic infection in patients with HIV/AIDS. Furthermore, Pneumocystis pneumonia is a feared complication of the immunosuppressive drug regimens used to treat autoimmunity, malignancy, and post-transplantation rejection. With an increasing at-risk population, there is a strong need for novel approaches to discover diagnostic and vaccine targets. There are multiple challenges to finding these targets, however. First, Pneumocystis has a largely unannotated genome. To address this, we evaluated each protein encoded within the Pneumocystis genome to that of other fungi using NCBI Blast. Second, Pneumocystis relies on a multiphasic life cycle, as both the transmissible form, the ascus, and the replicative form, the troph, reside within the alveolar space of the host. Towards that end, we purified asci and trophs from Pneumocystis murina and utilized transcriptomics to identify differentially regulated genes. Two such genes, Arp9 and Sp, are differentially regulated in the ascus and the troph, respectively, and can be utilized to characterize the state of the Pneumocystis life cycle in vivo. Gsc1, a β-1,3-glucan synthase with a large extracellular domain previously identified using surface proteomics, was more highly expressed on the ascus form of Pneumocystis. GSC-1 ectodomain immunization generated a strong antibody response capable of recognizing the surface of the Pneumocystis asci. GSC-1 ectodomain immunization was also capable of reducing ascus burden following primary challenge with Pneumocystis murina. Finally, mice immunized with the GSC-1 ectodomain had limited burden following natural transmission of Pneumocystis using a co-housing model. Pneumocystis asci and trophs were separated via flow cytometry and the transcriptome was sequenced, allowing to further understand the differential expression of various RNA transcripts. These data can be mined for life-form specific diagnostics and therapeutic targets.
2019-08-24 | GSE136100 | GEO
Project description:Background. Pneumocystis jirovecii pneumonia (PCP) is a leading cause of fungal pneumonia, but its diagnosis primarily relies on invasive bronchoalveolar lavage (BAL) specimens that are difficult to obtain. Oropharyngeal swabs and serum could improve the PCP diagnostic workflow, and we hypothesized that CRISPR could enhance assay sensitivity to allow robust P. jirovecii diagnosis using swabs and serum. Herein we describe the development of an ultrasensitive RT-PCR-coupled CRISPR assay with high active-infection specificity in infant swabs and adult BAL and serum. Methods. Mouse analyses employed an RT-PCR CRISPR assay to analyze P. murina transcripts in wild-type and Rag2-/- mouse lung RNA, BAL, and serum at 2-, 4-, and 6-weeks post-infection. Human studies used an optimized RT-PCR CRISPR assay to detect P. jirovecii transcripts in infant oropharyngeal swab samples, adult serum, and adult BAL specimens from P. jirovecii-infected and P. jirovecii-non-infected patients. Results. The P. murina assays sensitively detected Pneumocystis RNA in the serum of infected mice throughout infection. Oropharyngeal swab CRISPR assay results identified infants infected with P. jirovecii with greater sensitivity (96.3% vs. 66.7%) and specificity (100% vs. 90.6%) than RT-qPCR compared to mtLSU standard marker, and CRISPR results achieved higher sensitivity than RT-qPCR results (93.3% vs. 26.7%) in adult serum specimens. Conclusion. Since swabs are routinely collected in pediatric pneumonia patients, serum is easier to obtain than BAL, and RT-PCR CRISPR results may not detect P. jirovecii colonization, this assay approach could improve pediatric Pneumocystis diagnosis by achieving specificity for active infection and avoiding the requirement for BAL specimens.
2025-03-17 | GSE289324 | GEO
Project description:Transcriptome of Pneumocystis jirovecii during human Pneumocystis pneumonia
| PRJEB370 | ENA
Project description:Pneumocystis pneumonia (PCP) is an opportunistic infectious disease prevalent in immunosuppressive host. Corticosteroids treatment is the most significant risk factor for HIV-negative patients with PCP, though little is known about how corticosteroids alters the host defense against Pneumocystis infection. In the present study, we used transcriptomic analysis to examine the immune response in the lung of dexamethasone-treated PCP mice and compare the immune reaction of them with those without dexamethasone treatment.
2016-05-03 | GSE80975 | GEO
Project description:Recent progress in unbiased metagenomic next-generation sequencing (mNGS) allows simultaneous examination of microbial and host genetic material in a single test. Leveraging affordable bronchoalveolar lavage fluid (BALF) mNGS data, we employed machine learning to create a diagnostic approach distinguishing lung cancer from pulmonary infections, conditions prone to misdiagnosis in clinical settings. This prospective study analyzed BALF-mNGS data from lung cancer and pulmonary infection patients, delineating differences in DNA/RNA microbial composition, bacteriophage abundances, and host responses, including gene expression, transposable element levels, immune cell composition, and tumor fraction derived from copy number variation (CNV). Integrating these metrics into a host/microbe metagenomics-driven machine learning model (Model VI) demonstrated robustness, achieving an AUC of 0.87 (95% CI = 0.857-0.883), sensitivity = 73.8%, and specificity = 84.5% in the training cohort, and an AUC of 0.831 (95% CI = 0.819-0.843), sensitivity = 67.1%, and specificity = 94.4% in the validation cohort for distinguishing lung cancer from pulmonary infections. The application of a rule-in and rule-out strategy-based composite predictive model significantly enhances accuracy (ACC) in distinguishing between lung cancer and tuberculosis (ACC=0.913), fungal infection (ACC=0.955), and bacterial infection (ACC=0.836). These findings highlight the potential of cost-effective mNGS-based analysis as a valuable tool for early differentiation between lung cancer and pulmonary infections, offering significant benefits through a single comprehensive testing.
2024-01-08 | GSE252118 | GEO
Project description:In wild-type mice, expression of chemokines that are ligands for Ccr2, Cxcr3, and Cxcr2 increased at days 32 to 41 post-infection, with a return to baseline by day 75. Concomitant increases were seen in Ccr2 and Cxcr3 but not in Cxcr2 expression. Induction of these same factors also occurred in CD40-ligand and CD40 knockout mice but only at a much later time-point, during uncontrolled Pneumocystis pneumonia (PCP). Expression of CD4 Th1 markers was increased in wild-type mice during clearance of infection. Ccr2 and Cx3cr1 knockout mice cleared Pneumocystis infection with kinetics similar to wild-type mice, and all animals developed anti-Pneumocystis antibodies. Upregulation of Ccr2 and Cxcr3 and their ligands supports an important role for T helper cells and mononuclear phagocytes in the clearance of Pneumocystis infection. However, based on the current and prior studies, no single chemokine receptor appears to be critical to the clearance of Pneumocystis.
2015-10-10 | GSE67720 | GEO
Project description:In wild-type mice, expression of chemokines that are ligands for Ccr2, Cxcr3, and Cxcr2 increased at days 32 to 41 post-infection, with a return to baseline by day 75. Concomitant increases were seen in Ccr2 and Cxcr3 but not in Cxcr2 expression. Induction of these same factors also occurred in CD40-ligand and CD40 knockout mice but only at a much later time-point, during uncontrolled Pneumocystis pneumonia (PCP). Expression of CD4 Th1 markers was increased in wild-type mice during clearance of infection. Ccr2 and Cx3cr1 knockout mice cleared Pneumocystis infection with kinetics similar to wild-type mice, and all animals developed anti-Pneumocystis antibodies. Upregulation of Ccr2 and Cxcr3 and their ligands supports an important role for T helper cells and mononuclear phagocytes in the clearance of Pneumocystis infection. However, based on the current and prior studies, no single chemokine receptor appears to be critical to the clearance of Pneumocystis.
2015-10-10 | GSE67718 | GEO