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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 01, 2021 |
| Title |
Gene expression signatures to the radiation attenuated Schistosome Vaccine |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The radiation-attenuated (RA) cercarial vaccine is still the best model eliciting high protection levels, although the immune mechanisms have not yet been fully characterized. In order to identify genes and pathways underlying protection we investigated patterns of gene expression in PBMC and skin draining Lymph Nodes (LN) from mice using two exposure comparisons: vaccination with 500 attenuated cercariae versus infection with 500 normal cercariae; one versus three doses. Vaccinated mice were challenged with 120 normal parasites. Integration of PBMC and LN data from the infected group revealed early up-regulation of pathways associated with Th2 skewing and polarization of IgG antibody profiles. Additionally, hemostasis pathways were downregulated in infected mice, correlating with platelet reduction, potentially a mechanism to assist parasite migration through capillary beds. Conversely, up regulation of such mechanisms after vaccination may explain parasite blockade in the lungs. In contrast, a single exposure to attenuated parasites revealed early establishment of a Th1 bias (signaling of IL-1, IFN-γ; and Leishmania infection). Genes encoding chemokines and their receptors were more prominent in vaccinated mice, indicating an enhanced capacity for inflammation, potentially augmenting the inhibition of intravascular migration. Increasing the vaccinations from one to three did not dramatically elevate protection, but there was a clear shift towards antibody-mediated effectors. However, elements of the Th1 bias were still evident. Notable features after three vaccinations were markers of cytotoxicity (including IL-6 and NK cells) together with growth factors and their receptors (FGFR/VEGF/EGF) and the apoptosis pathway. Indeed, there is evidence for the development of anergy after three vaccinations, borne out by the limited responses detected in samples after challenge. We infer that persistence of a Th1 response puts a limit on expression of antibody-mediated mechanisms. This feature may explain the failure of multiple doses to drive protection towards sterile immunity. We suggest that the secretions of lung stage parasites would make a novel cohort of antigens for testing in protection experiments.
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| Overall design |
Mice were vaccinated with one dose (V1) or three doses (V3) of 500 attenuated cercariae, or infected (VC) with 500 normal ceracriae. Then, gene expression in mice PBMC was measured in a time course manner at days 7 (7dpi) and 17 (17dpi) after vacination or infection. In addition, the vaccine groups (V1 and V3) and a challenge control (Chc) were challenge with 120 normal cercariae and PBMC gene expression was measured 7 days post-challenge (7dpc). PBMC from control (C) non-treated mice was used to generate the baseline of gene expression. Four to five independent biological replicates were assessed per group (V1, V3, VC and Chc) per time point, and 16 biological replicates from control group (C) were used to generate the baseline of expression for PBMC microarray analysis. All biological replicate consisted of a pool of PBMCs (containing equal amounts of total RNA) from three mice. Data is derived from one independent experiment. Gene expression in mice skin draining lymph nodes (sdLN) was measured in an independent assay 5 days (5dpi) after one vaccine dose (V1) or three vaccine doses (V3) of 500 attenuated cercariae, or after infection (VC) with 500 normal ceracriae. Three independent biological replicates were assessed per group for sdLN microarray analysis, in which each biological replicate consisted of a pool of sdLNs from three mice. Data is derived from one independent experiment.
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| Contributor(s) |
Farias LP, Vitoriano-Souza J, Cardozo LE, Gama LR, Almeida GT, Verjovski-Almeida S, Nakaya HI, Leite LC |
| Citation(s) |
33777004 |
| Submission date |
Dec 31, 2020 |
| Last update date |
Apr 06, 2021 |
| Contact name |
Leonardo Paiva Farias |
| Organization name |
Instituto Gonçalo Moniz-Fiocruz
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| Lab |
LIB
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| Street address |
Rua Waldemar Falcão, 121
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| City |
Salvador |
| State/province |
Bahia |
| ZIP/Postal code |
40296-710 |
| Country |
Brazil |
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| Platforms (1) |
| GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
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| Samples (67)
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| Relations |
| BioProject |
PRJNA688890 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE164094_RAW.tar |
223.7 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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