Signatures of B cell receptor repertoire following Pneumocystis infection
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ABSTRACT:
PROVIDER: PRJNA682167 | ENA |
REPOSITORIES: ENA
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Project description:B cells play vital roles in host defense against Pneumocystis infection, however, the features of B cell receptor (BCR) repertoire in the disease progression remain unclear. Here we integrated single-cell RNA sequencing and single-cell BCR sequencing of immune cells from mice lung at uninfected state and 1-4 weeks postinfection, in order to illustrate the dynamic nature of B cell responses during Pneumocystis infection. We identified continuously increased plasma cells and an elevated ratio of (IgA+ IgG) to (IgD+ IgM) after infection. Moreover, Pneumocystis infection was associated with an increase of a naïve B subset characterized by elevated expression of the transcription factor ATF3. The proportion of clonal expanded cells progressively increased, with the BCR diversity decreased. Biased usage of V(D)J genes was observed, and the usage frequency of IGHV9-3 was elevated. Overall, these results present a detailed atlas of B cell transcriptional changes and BCR repertoire features in the context of Pneumocystis infection.
2021-04-28 | GSE162533 | GEO
Project description:T cell response exert critical roles in the host adaptive immunity against Pneumocystis. However, the dynamics and diversity of T cell immune repertoire in HIV-negative Pneumocystis remains unknown. In this study, single-cell RNA and T cell receptor (TCR) sequencing were applied on cells sorted from lung tissues of mice infected with Pneumocystis from 0 to 4 weeks. Our data demonstrated clonally CD4+ T cells and CD8+ T cells expanded in response to Pneumocystis, which marked by highly expressed genes associated with T cell activation and cytotoxicity. The length distribution of CDR3 AA and gene usage variability were similar between Pneumocystis infected mice and control group. We tracked the transcriptome and TCR immune repertoires profiles of expanded lymphocyte clones during Pneumocystis infection, which demonstrate a reconstitution of the TCR immune repertoire after Pneumocystis infection.
2021-03-26 | GSE156843 | GEO
Project description: Not available
| S-EPMC8202503 | biostudies-literature
Project description:Type I IFN-signaling suppresses an excessive IFN-{gamma} response and prevents lung damage and chronic inflammation following Pneumocystis (PC)-infection and clearance in CD4 T cell-competent mice. Type I IFN -signaling in pulmonary CD11c+ DCs and alveolar macrophages may prevent chronic inflammation following PC lung infection and clearance by suppressing an excessive IFN-g-response via the induction of SOCS1. IFNAR-/- and wildtype mice were both Pneumocystis infected via itratracheal instillation. Pulmonary CD11c+ cells were isolated from collagen digested lungs at day 7 and day 14 post infection from both wildtype and IFNAR-/- mice using a magnetic cell sorting technique from Miltenyi with CD11c microbeads. Cells from three individual animals per group were isolated and assessed. Comparison of 2 treatment types at 2 timepoints to determine whether type I IFN signaling is initiated in resident and early recruited pulmonary CD11c+ cells following Pneumocystis lung infection and whether this is relevant to the outcome of the inflammatory response during the initiation of clearance.
2010-07-07 | E-GEOD-18607 | biostudies-arrayexpress
Project description:Type I IFN-signaling suppresses an excessive IFN-{gamma} response and prevents lung damage and chronic inflammation following Pneumocystis (PC)-infection and clearance in CD4 T cell-competent mice. Type I IFN -signaling in pulmonary CD11c+ DCs and alveolar macrophages may prevent chronic inflammation following PC lung infection and clearance by suppressing an excessive IFN-g-response via the induction of SOCS1.
2010-07-07 | GSE18607 | 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
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:With a filter of false-discovery rate less than 0.1 and fold change greater than 1.5, 115 genes were found to be up- and 137 were down-regulated in alveolar macrophages during Pneumocystis carinii infection. Total RNA samples from 4 each of normal, dexamethasone-treated, and Pneumocystis carinii-infected Sprague-Dawley rats were analyzed by the Affymetrix GeneChip RG-U34A
2010-04-12 | E-GEOD-20149 | biostudies-arrayexpress
Project description:We performed single-cell transcriptome and antibody repertoire sequencing of bone marrow plasma cells following protein (OVA and TNFR2) immunizations or infection with high dose LCMV clone 13.
2021-12-01 | E-MTAB-11096 | biostudies-arrayexpress