Dados do Trabalho

Título

Gene co-expression analysis of cutaneous leishmaniasis uncovered a potential role for miRs in lesion development

Introdução

Cutaneous Leishmaniasis (CL) is characterized by ulcerative skin lesions, leading to severe and permanent scarring. Previous studies have provided extensive transcriptome datasets of human skin lesions caused by Leishmania braziliensis (Lb), highlighting crucial aspects of immunopathology. To understand CL's early infection stages, disease progression, and healing process, we profiled lesions and draining lymph nodes (dLNs) transcriptomes using a murine model that mimics Lb disease in humans.

Objetivo (s)

The objective of this study was to compare the transcriptional profiles of murine and human diseases during the chronic phase (ulceration) and identify the signatures associated with the early and late stages of experimental CL.

Material e Métodos

BALB/C mice were infected with Lb in their ears. Infected ears and draining lymph nodes (dLN) were collected at multiple time points: 2, 6, and 48 hours, and 14, 35, and 77 days after infection. Three biological replicates per time-point were used for both tissues, and bulk RNA-seq was performed. CEMItool was used to identify gene modules (M) with significant co-expression throughout lesion development.

Resultados e Conclusão

Results: Gene co-expression analysis revealed dynamic changes occurring shortly after the inoculation of Lb into the dermis, continuing until lesion healing. During the early phase of lesion development, we observed peak activation of a wound healing module (M1 Apical junction) at 6h and Day 14, as well as an inflammatory module (M2 LXR/RXR) at 2-6h. In the late phase of lesion development, there was significant activation of inflammatory modules involved in Phagosome formation (M3) and LXR/RXR (M2), reaching their peak at Day 35-77. Surprisingly, a distinct module (M4) composed of 63% unclassified genes, 23.3% long non-conding RNAs and 11% pseudogenes, exhibited marked deactivation at Day 35. Additionally, at Day 77, we observed the emergence of immunoglobulins module (M6). Furthermore, our analysis unveiled the presence of a group of microRNAs that have been previously reported in the literature to be involved in the regulation of inflammation and tissue remodeling. Altogether, the transcriptomic profile provided here highlights previous and new pathways associated to Lb infection, which could lead to new avenues for therapeutic interventions as the use of miR mimics and inhibitors.

Palavras-chave

Leishmaniasis, RNAseq, immune response

Agradecimentos

CAPES, PIAP/IGM/FIOCRUZ-BA (001/2017)