Gene expression profiling specifies chemokine, mitochondrial and lipid metabolism signatures in leprosy.
Herein, we performed microarray experiments in Schwann cells infected with live M. leprae and identified novel differentially expressed genes (DEG) in M. leprae infected cells. Also, we selected candidate genes associated or implicated with leprosy in genetic studies and biological experiments. Fort...
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2013
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oai:doaj.org-article:58cb7e797f8b4d1ab03913facd9c320a2021-11-18T07:41:45ZGene expression profiling specifies chemokine, mitochondrial and lipid metabolism signatures in leprosy.1932-620310.1371/journal.pone.0064748https://doaj.org/article/58cb7e797f8b4d1ab03913facd9c320a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23798993/?tool=EBIhttps://doaj.org/toc/1932-6203Herein, we performed microarray experiments in Schwann cells infected with live M. leprae and identified novel differentially expressed genes (DEG) in M. leprae infected cells. Also, we selected candidate genes associated or implicated with leprosy in genetic studies and biological experiments. Forty-seven genes were selected for validation in two independent types of samples by multiplex qPCR. First, an in vitro model using THP-1 cells was infected with live Mycobacterium leprae and M. bovis bacillus Calmette-Guérin (BCG). In a second situation, mRNA obtained from nerve biopsies from patients with leprosy or other peripheral neuropathies was tested. We detected DEGs that discriminate M. bovis BCG from M. leprae infection. Specific signatures of susceptible responses after M. leprae infection when compared to BCG lead to repression of genes, including CCL2, CCL3, IL8 and SOD2. The same 47-gene set was screened in nerve biopsies, which corroborated the down-regulation of CCL2 and CCL3 in leprosy, but also evidenced the down-regulation of genes involved in mitochondrial metabolism, and the up-regulation of genes involved in lipid metabolism and ubiquitination. Finally, a gene expression signature from DEG was identified in patients confirmed of having leprosy. A classification tree was able to ascertain 80% of the cases as leprosy or non-leprous peripheral neuropathy based on the expression of only LDLR and CCL4. A general immune and mitochondrial hypo-responsive state occurs in response to M. leprae infection. Also, the most important genes and pathways have been highlighted providing new tools for early diagnosis and treatment of leprosy.Luana Tatiana Albuquerque GuerreiroAnna Beatriz Robottom-FerreiraMarcelo Ribeiro-AlvesThiago Gomes Toledo-PintoTiana Rosa BritoPatrícia Sammarco RosaFelipe Galvan SandovalMárcia Rodrigues JardimSérgio Gomes AntunesEdward J ShannonEuzenir Nunes SarnoMaria Cristina Vidal PessolaniDiana Lynn WilliamsMilton Ozório MoraesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e64748 (2013) |
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Medicine R Science Q Luana Tatiana Albuquerque Guerreiro Anna Beatriz Robottom-Ferreira Marcelo Ribeiro-Alves Thiago Gomes Toledo-Pinto Tiana Rosa Brito Patrícia Sammarco Rosa Felipe Galvan Sandoval Márcia Rodrigues Jardim Sérgio Gomes Antunes Edward J Shannon Euzenir Nunes Sarno Maria Cristina Vidal Pessolani Diana Lynn Williams Milton Ozório Moraes Gene expression profiling specifies chemokine, mitochondrial and lipid metabolism signatures in leprosy. |
| description |
Herein, we performed microarray experiments in Schwann cells infected with live M. leprae and identified novel differentially expressed genes (DEG) in M. leprae infected cells. Also, we selected candidate genes associated or implicated with leprosy in genetic studies and biological experiments. Forty-seven genes were selected for validation in two independent types of samples by multiplex qPCR. First, an in vitro model using THP-1 cells was infected with live Mycobacterium leprae and M. bovis bacillus Calmette-Guérin (BCG). In a second situation, mRNA obtained from nerve biopsies from patients with leprosy or other peripheral neuropathies was tested. We detected DEGs that discriminate M. bovis BCG from M. leprae infection. Specific signatures of susceptible responses after M. leprae infection when compared to BCG lead to repression of genes, including CCL2, CCL3, IL8 and SOD2. The same 47-gene set was screened in nerve biopsies, which corroborated the down-regulation of CCL2 and CCL3 in leprosy, but also evidenced the down-regulation of genes involved in mitochondrial metabolism, and the up-regulation of genes involved in lipid metabolism and ubiquitination. Finally, a gene expression signature from DEG was identified in patients confirmed of having leprosy. A classification tree was able to ascertain 80% of the cases as leprosy or non-leprous peripheral neuropathy based on the expression of only LDLR and CCL4. A general immune and mitochondrial hypo-responsive state occurs in response to M. leprae infection. Also, the most important genes and pathways have been highlighted providing new tools for early diagnosis and treatment of leprosy. |
| format |
article |
| author |
Luana Tatiana Albuquerque Guerreiro Anna Beatriz Robottom-Ferreira Marcelo Ribeiro-Alves Thiago Gomes Toledo-Pinto Tiana Rosa Brito Patrícia Sammarco Rosa Felipe Galvan Sandoval Márcia Rodrigues Jardim Sérgio Gomes Antunes Edward J Shannon Euzenir Nunes Sarno Maria Cristina Vidal Pessolani Diana Lynn Williams Milton Ozório Moraes |
| author_facet |
Luana Tatiana Albuquerque Guerreiro Anna Beatriz Robottom-Ferreira Marcelo Ribeiro-Alves Thiago Gomes Toledo-Pinto Tiana Rosa Brito Patrícia Sammarco Rosa Felipe Galvan Sandoval Márcia Rodrigues Jardim Sérgio Gomes Antunes Edward J Shannon Euzenir Nunes Sarno Maria Cristina Vidal Pessolani Diana Lynn Williams Milton Ozório Moraes |
| author_sort |
Luana Tatiana Albuquerque Guerreiro |
| title |
Gene expression profiling specifies chemokine, mitochondrial and lipid metabolism signatures in leprosy. |
| title_short |
Gene expression profiling specifies chemokine, mitochondrial and lipid metabolism signatures in leprosy. |
| title_full |
Gene expression profiling specifies chemokine, mitochondrial and lipid metabolism signatures in leprosy. |
| title_fullStr |
Gene expression profiling specifies chemokine, mitochondrial and lipid metabolism signatures in leprosy. |
| title_full_unstemmed |
Gene expression profiling specifies chemokine, mitochondrial and lipid metabolism signatures in leprosy. |
| title_sort |
gene expression profiling specifies chemokine, mitochondrial and lipid metabolism signatures in leprosy. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/58cb7e797f8b4d1ab03913facd9c320a |
| work_keys_str_mv |
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