Comparison of single cell RNA sequencing in leprosy lesions from lepromatous and reversal reaction patients
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ABSTRACT:
PROVIDER: PRJNA636282 | ENA |
REPOSITORIES: ENA
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Project description:Effective innate immunity against many microbial pathogens requires macrophage programs that upregulate phagocytosis and direct antimicrobial pathways, two functions generally assumed to be coordinately regulated. Here the regulation of these key functions was investigated in human blood-derived macrophages. IL-10 induced the phagocytic pathway, including CD209 and scavenger receptors, resulting in phagocytosis of mycobacteria and oxLDL. IL-15 induced the vitamin D-dependent antimicrobial pathway and CD209, yet the cells were less phagocytic. The differential regulation of macrophage functional programs was confirmed by analysis of the spectrum of leprosy lesions: the macrophage phagocytosis pathway was prominent in the clinically progressive, multibacillary form, whereas the vitamin D-dependent antimicrobial pathway predominated in the self-limited form of the disease and in patients undergoing reversal reactions from the multibacillary to the self-limited form. These data indicate that macrophage programs for phagocytosis and antimicrobial responses are distinct and differentially regulated in innate immunity in bacterial infections. Experiment Overall Design: 7 LL lesions, 10 BT lesions, 7 RR lesions
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Project description:Skin biopsy specimens of skin lesions were profiled for miRNA expression. In this study, we indentified miRNA species that were differentially expressed in the skin lesions of either the lepromatous or tuberculoid forms of leprosy. One miRNA species, hsa-mir-21, found in the lepromatous lesions was capable of downregulating the vitamin D-dependent antimicrobial pathway. Scalpel or punch skin biopsy specimens were obtained after informed consent from patients with tuberculoid leprosy and patients with lepromatous leprosy at the time of diagnosis. Specimens were embedded in OCT medium, snap-frozen in liquid nitrogen and stored at 80°C until sectioning.
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Project description:In this study, a comprehensive assessment of human mRNA was performed on leprosy skin lesions using DNA chip microarrays, which included the entire spectrum of the disease along with its reactional states. Sixty-six samples from leprotic lesions (10TT, 10BT, 10BB, 10BL, 4LL, 14R1, and 10R2) and nine skin biopsies from healthy individuals were used as controls (CC) (ages ranged from 06 to 83 years, 48 were male and 29 female). The evaluation identified differentially expressed mRNAs [Fold Change (FC)â¥2.0, p<0.05] in disease lesions versus healthy controls or between them. Some of these genes were validated by RT-PCR and/or immunohistochemistry. The sequence of events for this study followed the order below. Patients who were treated for leprosy were examined by leprologists and submitted to two biopsy procedures. One biopsy was processed for histopathological analysis, bacilloscopy and immunohistochemistry (IHC), the other was immediately stored in RNAlater® solution (Ambion) for further RNA extraction. Sixty-eight samples from leprotic lesions (10TT, 10BT, 10BB, 10BL, 4LL, 14R1, and 10R2) were selected for analysis. In addition, nine skin biopsies from healthy individuals were usedas controls (CC). Differentially expressed genes identified in the cDNA microarray assay were validated by quantitative RT-PCR and IHC.
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