Pneumocystis jirovecii
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA782857 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transcriptome of Pneumocystis jirovecii during human Pneumocystis pneumonia
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Project description:β-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis. In the current study we examined whether β-1,3 glucans are masked by surface proteins in Pneumocystis, and what role β-glucans play in Pneumocystis-associated inflammation. For 3 species, including P. jirovecii, which causes Pneumocystis pneumonia (PCP) in humans, P. carinii, and P. murina, β-1,3 glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment. Using Q-PCR and microarray techniques, we demonstrated in a mouse model of PCP that treatment with caspofungin, an inhibitor of β-1,3 glucan synthesis, for 21 days, decreased expression of a broad panel of inflammatory markers, including IFN-γ, TNF-α, IL-1β, IL-6, and multiple chemokines/chemokine ligands. Thus, β-glucans in Pneumocystis cysts are largely masked, which likely decreases innate immune activation; this mechanism presumably was developed for interactions with immunocompetent hosts, in whom organism loads are substantially lower. In immunosuppressed hosts with a high organism burden, organism death and release of glucans appears to be an important contributor to deleterious host inflammatory responses.
2016-08-31 | GSE79079 | 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:Pathogenic fungus that causes pneumonia in immunocompromised persons
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Project description:Pneumocystis carinii bisulfite_seq
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