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dc.contributor.authorCarmelo, Emma 
dc.contributor.authorOntoria, Eduardo
dc.contributor.authorHernández-Santana, Yasmina E.
dc.contributor.authorGonzález-García, Ana C.
dc.contributor.authorLópez, Manuel C.
dc.contributor.authorValladares Hernández, Basilio 
dc.contributor.otherObstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología y Medicina Legal y Forense y Parasitología
dc.contributor.otherInvestigación en Parasitología
dc.date.accessioned2024-04-25T20:05:52Z
dc.date.available2024-04-25T20:05:52Z
dc.date.issued2018
dc.identifier.urihttp://riull.ull.es/xmlui/handle/915/37287
dc.description.abstractLeishmania spp. is a protozoan parasite that affects millions of people around the world. At present, there is no effective vaccine to prevent leishmaniases in humans. A major limitation in vaccine development is the lack of precise understanding of the particular immunological mechanisms that allow parasite survival in the host. The parasite-host cell interaction induces dramatic changes in transcriptome patterns in both organisms, therefore, a detailed analysis of gene expression in infected tissues will contribute to the evaluation of drug and vaccine candidates, the identification of potential biomarkers, and the understanding of the immunological pathways that lead to protection or progression of disease. In this large-scale analysis, differential expression of 112 immune-related genes has been analyzed using high-throughput qPCR in spleens of infected and naïve Balb/c mice at four different time points. This analysis revealed that early response against Leishmania infection is characterized by the upregulation of Th1 markers and M1-macrophage activation molecules such as Ifng, Stat1, Cxcl9, Cxcl10, Ccr5, Cxcr3, Xcl1, and Ccl3. This activation doesn’t protect spleen from infection, since parasitic burden rises along time. This marked difference in gene expression between infected and control mice disappears during intermediate stages of infection, probably related to the strong anti-inflammatory and immunosuppresory signals that are activated early upon infection (Ctla4) or remain activated throughout the experiment (Il18bp). The overexpression of these Th1/M1 markers is restored later in the chronic phase (8 wpi), suggesting the generation of a classical “protective response” against leishmaniasis. Nonetheless, the parasitic burden rockets at this timepoint. This apparent contradiction can be explained by the generation of a regulatory immune response characterized by overexpression of Ifng, Tnfa, Il10, and downregulation Il4 that counteracts the Th1/M1 response. This large pool of data was also used to identify potential biomarkers of infection and parasitic burden in spleen, on the bases of two different regression models. Given the results, gene expression signature analysis appears as a useful tool to identify mechanisms involved in disease outcome and to establish a rational approach for the identification of potential biomarkers useful for monitoring disease progression, new therapies or vaccine development.en
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.relation.ispartofseriesFrontiers in Cellular and Infection Microbiology, 8:197
dc.rightsLicencia Creative Commons (Reconocimiento-No comercial-Sin obras derivadas 4.0 Internacional)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ES
dc.titleTranscriptional Profiling of Immune-Related Genes in Leishmania infantum-Infected Mice: Identification of Potential Biomarkers of Infection and Progression of Diseaseen
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.3389/fcimb.2018.00197
dc.subject.keywordLeishmania infantumen
dc.subject.keywordtranscriptional profilingen
dc.subject.keywordhigh-throughput qPCRen
dc.subject.keywordimmune responsesen
dc.subject.keywordregression modelsen
dc.subject.keywordbiomarkersen


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