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| Status |
Public on Oct 25, 2022 |
| Title |
Pulmonary parasite infection: do trypanosomes take your breath away? |
| Platform organism |
Homo sapiens |
| Sample organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Approximately 20% of sleeping sickness patients exhibit respiratory complications which are commonly attributed to secondary bacterial infections, with an unknown role of the parasite. Using a Glossina morsitans tsetse fly initiated Trypansoma brucei infection in mice we found that parasites rapidly and permanently colonize the lungs, representing one of the major target organs next to the adipose tissue. Trypanosomes were found by immunofluorescence staining and scanning electron microscopy to occupy the extravascular spaces surrounding the blood vessels of the alveoli and bronchi. Parasites were even found in the lung cartilage. Trypanosomes were often observed as nests of multiplying parasites exhibiting close interactions with collagen and highly active secretion of extracellular vesicles that are engaged in intercellular communication. The local immune response was analysed by flow cytometry after 10 and 21 days of infection and was characterized by a substantial increase of CD11b+ Ly6C+ monocytes, CD11b+ Ly6C+ F4/80+ macrophages and CD11b+ CD11c+ dendritic cells. CD11b+ Ly6G+ neutrophils only accumulated prominently at the late infection time point. Interestingly, parasite presence resulted in a significant reduction of B220+ IgM+ B cells, CD11b+ CD11clo/- SiglecF+ eosinophils and TcR-β- NK1.1+ natural killer cells. Digital transcriptomics revealed infection-induced upregulation of Il-10, IFN-ɣ- and IFN-α-responses, IL-2-, IL-6- and TNF-signalling, a Th1 pro-inflammatory signature, negative immune checkpoint regulators and a predominant M1 macrophage polarization. Il12a and genes associated with complement and the B cell receptor were downregulated. No infection-associated pulmonary dysfunction could be detected by in vivo lung function measurements, mirroring the limited pulmonary complications during sleeping sickness. However, the substantial reduction of eosinophils, B cells and NK cells may render individuals more susceptible to opportunistic infections. Collectively, these observations provide essential insights in the peculiar parasite biology, immunological reactions and physiological function of a largely overlooked target organ which may trigger new diagnostic approaches for sleeping sickness.
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| Overall design |
C57BL/6JRj mice were kept in quarantine for at least 5 days before infection and were randomly allocated to the experimental units. Trypanosoma brucei brucei AnTAR1 were used for infection and total RNA from lung tissue extracted at 10dpi and 21 dpi.
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| Contributor(s) |
Van Weyenbergh J, Caljon G |
| Citation(s) |
36400767 |
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| Submission date |
Sep 02, 2022 |
| Last update date |
Dec 09, 2022 |
| Contact name |
Johan Van Weyenbergh |
| E-mail(s) |
j.vw@live.be
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| Phone |
+3216321390
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| Organization name |
KU Leuven
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| Department |
DMIT
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| Street address |
Herestraat 49
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| City |
Leuven |
| ZIP/Postal code |
3000 |
| Country |
Belgium |
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| Platforms (1) |
| GPL32631 |
NanoString nCounter Mouse Host Response V1.0 Panel |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA876276 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE212622_RawData_LungTryp_NS_MM_HOSTRESPONSE_V1.0.csv.gz |
25.0 Kb |
(ftp)(http) |
CSV |
| Processed data included within Sample table |
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