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Transcriptional profiling of immune-related genes in Leishmania infantum-infected mice: identification of potential biomarkers of infection and progression of disease

ABSTRACT: Transcriptional profiling of immune-related genes in Leishmania infantum-infected mice: identification of potential biomarkers of infection and progression of disease

PROVIDER: PRJNA439400 | ENA |

REPOSITORIES: ENA

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Project description:Leishmania 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. High-throughput real-time quantitative PCR is a highly sensitive, and specific technique that allows analysis of gene expression in multiple genes at the same time. Hence, it is an interesting approach that may bring light to this complex topic. In this large-scale analysis, forty-seven BALB/c mice were divided in two groups: control mice and mice infected with L. infantum promastigotes. After infection animals were sacrificed at different timepoints, RNA was purified from spleens and expression of 112 genes related with immune system was determined by high-throughput qPCR. These extensive gene-expression analyses reveal a selective recruitment of lymphocytes to the spleen and an immunosuppressive response, which favors parasite persistence, in early stages of the infection. In later stages of infection, gene-expression patterns suggest an inflammatory process that should resolve infection. Nevertheless, a detailed analysis reveals that L. infantum infection induces a regulatory process that counteracts the Th1/M1 response. This large pool of data was also used to identify a group of potential biomarkers of infection and parasitic burden in spleen, on the bases of two different statistical models, a logistic regression analysis and a linear regression analysis. Given the results, it seems clear that gene expression signature analysis is a useful tool to identify the 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 in Leishmaniases.

Project description:Leishmania 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. High-throughput real-time quantitative PCR is a highly sensitive, and specific technique that allows analysis of gene expression in multiple genes at the same time. Hence, it is an interesting approach that may bring light to this complex topic. In this large-scale analysis, forty-seven BALB/c mice were divided in two groups: control mice and mice infected with L. infantum promastigotes. After infection animals were sacrificed at different timepoints, RNA was purified from spleens and expression of 112 genes related with immune system was determined by high-throughput qPCR. These extensive gene-expression analyses reveal a selective recruitment of lymphocytes to the spleen and an immunosuppressive response, which favors parasite persistence, in early stages of the infection. In later stages of infection, gene-expression patterns suggest an inflammatory process that should resolve infection. Nevertheless, a detailed analysis reveals that L. infantum infection induces a regulatory process that counteracts the Th1/M1 response. Given the results, it seems clear that gene expression signature analysis is a useful tool to identify the 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 in Leishmaniases.

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Transcriptional profiling of immune-related genes in Leishmania infantum-infected mice: identification of potential biomarkers of infection and progression of disease

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