Meta-transcriptome Profiling of the Human-Leishmania braziliensis Cutaneous Lesion
| Autor: | Sara Passos, Fernanda O. Novais, Laura A. L. Dillon, Lucas P. Carvalho, Edgar M. Carvalho, V. K. Hughitt, Stephen M. Christensen, Najib M. El-Sayed, Phillip Scott, Daniel P. Beiting, David M. Mosser |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Gene Expression Pathogenesis Pathology and Laboratory Medicine Lymphocyte Activation Transcriptome Mathematical and Statistical Techniques 0302 clinical medicine Zoonoses Gene expression Medicine and Health Sciences Parasite hosting Leishmaniasis Immune Response Skin Principal Component Analysis lcsh:Public aspects of medicine Genomics 3. Good health Infectious Diseases Host-Pathogen Interactions Physical Sciences Transcriptome Analysis Statistics (Mathematics) Research Article Neglected Tropical Diseases medicine.medical_specialty lcsh:Arctic medicine. Tropical medicine lcsh:RC955-962 Immunology 030231 tropical medicine Leishmaniasis Cutaneous Biology Research and Analysis Methods Leishmania braziliensis Host-Parasite Interactions 03 medical and health sciences Signs and Symptoms Cutaneous leishmaniasis Diagnostic Medicine Molecular genetics Genetics Parasitic Diseases medicine Humans Statistical Methods Gene Protozoan Infections Gene Expression Profiling Macrophages Public Health Environmental and Occupational Health Biology and Life Sciences Computational Biology Correction lcsh:RA1-1270 DNA Protozoan Tropical Diseases Genome Analysis biology.organism_classification medicine.disease Molecular biology Gene expression profiling 030104 developmental biology Case-Control Studies Multivariate Analysis Lesions Mathematics |
| Zdroj: | PLoS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, Vol 10, Iss 9, p e0004992 (2016) |
| ISSN: | 1935-2735 |
| Popis: | Host and parasite gene expression in skin biopsies from Leishmania braziliensis-infected patients were simultaneously analyzed using high throughput RNA-sequencing. Biopsies were taken from 8 patients with early cutaneous leishmaniasis and 17 patients with late cutaneous leishmaniasis. Although parasite DNA was found in all patient lesions at the time of biopsy, the patients could be stratified into two groups: one lacking detectable parasite transcripts (PTNeg) in lesions, and another in which parasite transcripts were readily detected (PTPos). These groups exhibited substantial differences in host responses to infection. PTPos biopsies contained an unexpected increase in B lymphocyte-specific and immunoglobulin transcripts in the lesions, and an upregulation of immune inhibitory molecules. Biopsies without detectable parasite transcripts showed decreased evidence for B cell activation, but increased expression of antimicrobial genes and genes encoding skin barrier functions. The composition and abundance of L. braziliensis transcripts in PTPos lesions were surprisingly conserved among all six patients, with minimal meaningful differences between lesions from patients with early and late cutaneous leishmaniasis. The most abundant parasite transcripts expressed in lesions were distinct from transcripts expressed in vitro in human macrophage cultures infected with L. amazonensis or L. major. Therefore in vitro gene expression in macrophage monolayers may not be a strong predictor of gene expression in lesions. Some of the most highly expressed in vivo transcripts encoded amastin-like proteins, hypothetical genes, putative parasite virulence factors, as well as histones and tubulin. In summary, RNA sequencing allowed us to simultaneously analyze human and L. braziliensis transcriptomes in lesions of infected patients, and identify unexpected differences in host immune responses which correlated with active transcription of parasite genes. Author Summary Leishmania spp are intracellular protozoan parasites that replicate primarily within host tissue macrophages. In this paper we simultaneously query host and parasite gene expression in human cutaneous L. braziliensis lesions. We observe an unexpectedly prominent role for B cells and immunoglobulins in lesions in which actively transcribing parasites reside. We also observe that parasite gene expression is surprisingly conserved among L. braziliensis lesions, and the genes that are expressed in lesions are not those that have been previously associated with parasite growth in vitro. This analysis of parasite and host gene expression in lesions may lead to the identification of new parasite virulence factors and may identify host responses that promote parasite persistence in lesions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|