RT info:eu-repo/semantics/article
T1 Transcriptional Profiling of
Immune-Related Genes in
Leishmania infantum-Infected Mice:
Identification of Potential Biomarkers
of Infection and Progression of
Disease
A1 Carmelo Pascual, Emma
A1 Ontoria, Eduardo
A1 Hernández-Santana, Yasmina E.
A1 González-García, Ana C.
A1 López, Manuel C.
A1 Valladares Hernández, Basilio
A2 Obstetricia y GinecologíaPediatría, Medicina Preventiva y Salud Pública, Toxicología y Medicina Legal y Forense y Parasitología
A2 Investigación en Parasitología
K1 Leishmania infantum
K1 transcriptional profiling
K1 high-throughput qPCR
K1 immune responses
K1 regression models
K1 biomarkers
AB Leishmania spp. is a protozoan parasite that affects millions of people around theworld. At present, there is no effective vaccine to prevent leishmaniases in humans.A major limitation in vaccine development is the lack of precise understanding ofthe particular immunological mechanisms that allow parasite survival in the host. Theparasite-host cell interaction induces dramatic changes in transcriptome patterns inboth organisms, therefore, a detailed analysis of gene expression in infected tissueswill contribute to the evaluation of drug and vaccine candidates, the identificationof potential biomarkers, and the understanding of the immunological pathways thatlead to protection or progression of disease. In this large-scale analysis, differentialexpression of 112 immune-related genes has been analyzed using high-throughputqPCR in spleens of infected and naïve Balb/c mice at four different time points. Thisanalysis revealed that early response against Leishmania infection is characterizedby the upregulation of Th1 markers and M1-macrophage activation molecules suchas Ifng, Stat1, Cxcl9, Cxcl10, Ccr5, Cxcr3, Xcl1, and Ccl3. This activation doesn’tprotect spleen from infection, since parasitic burden rises along time. This markeddifference in gene expression between infected and control mice disappears duringintermediate stages of infection, probably related to the strong anti-inflammatory andimmunosuppresory signals that are activated early upon infection (Ctla4) or remainactivated throughout the experiment (Il18bp). The overexpression of these Th1/M1markers is restored later in the chronic phase (8 wpi), suggesting the generationof a classical “protective response” against leishmaniasis. Nonetheless, the parasiticburden rockets at this timepoint. This apparent contradiction can be explained by thegeneration of a regulatory immune response characterized by overexpression of Ifng,Tnfa, Il10, and downregulation Il4 that counteracts the Th1/M1 response. This largepool of data was also used to identify potential biomarkers of infection and parasiticburden in spleen, on the bases of two different regression models. Given the results, gene expression signature analysis appears as a useful tool to identify mechanismsinvolved in disease outcome and to establish a rational approach for the identification ofpotential biomarkers useful for monitoring disease progression, new therapies or vaccinedevelopment.
PB .Frontiers Media SA.
SN 978-2-88963-3
YR 2020
FD 2020
LK http://riull.ull.es/xmlui/handle/915/37407
UL http://riull.ull.es/xmlui/handle/915/37407
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 29-jun-2024