Leprosy piRnome: exploring new possibilities for an old disease

Abstract

Leprosy, which is caused by the human pathogen Mycobacterium leprae , causes nerve damage, deformity and disability in over 200,000 people every year. Because of the long doubling time of M. leprae (13 days) and the delayed onset of detectable symptoms, which is estimated to be approximately 3–7 years after infection, there is always a large percentage of subclinically infected individuals in the population who will eventually develop the disease, mainly in endemic countries. piRNAs comprise the largest group of small noncoding RNAs found in humans, and they are distinct from microRNAs (miRNAs) and small interfering RNAs (siRNAs). piRNAs function in transposon silencing, epigenetic regulation, and germline development. The functional role of piRNAs and their associated PIWI proteins have started to emerge in the development of human cancers and viral infections, but their relevance to bacterial diseases has not been investigated. The present study reports the piRNome of human skin, revealing that all but one of the piRNAs examined are downregulated in leprosy skin lesions. Considering that one of the best characterized functions of piRNAs in humans is posttranscriptional mRNA silencing, their functions are similar to what we have described for miRNAs, including acting on apoptosis, M. leprae recognition and engulfment, Schwann cell (SC) demyelination, epithelial–mesenchymal transition (EMT), loss of sensation and neuropathic pain. In addition to new findings on leprosy physiopathology, the discovery of relevant piRNAs involved in disease processes in human skin may provide new clues for therapeutic targets, specifically to control nerve damage, a prominent feature of leprosy that has no currently available pharmaceutical treatment.

Blood RNA signature RISK4LEP predicts leprosy years before clinical onset

“…Similarly, other transcriptomic studies described leprosy biomarkers associated with leprosy but after occurrence of symptoms and using skin biopsies [ 53 , 63 , 88 , 89 ]. Serrano-Coll and colleagues showed that RT-qPCR of Oct-6 identified multibacillary (MB) patients (n=30) in Colombia with an AUC of 83.0% (89].…”

“…However, S-100 immunohistochemistry alone showed a better AUC (96.0%). Pinto et al investigated the expression of non-coding RNAs in leprosy patients (5 TT and 6 LL) from Brazil [89] and found five P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) that classified leprosy patients with an AUC of 90.0%. Jorge et al .…”

Mucus piRNAs profiles of Vibrio harveyi‐infected Cynoglossus semilaevis: A hint for fish disease monitoring

“…The result suggested that the seven piRNAs may be used as candidate biomarkers to identify health condition of C. semilaevis when exposure to V. harveyi , and there may be considerable amount of immune‐related piRNAs in fish. In other infection of vertebrates, piR‐27283 was found up‐regulated in human skin tissues infected with Mycobacterium leprae , serving as a potential biomarker, and piRNAs was found as possible determinants of macrophage function and nerve regeneration through interactions with IL6R and GAS6 (Pinto et al., 2020). Trypanosoma cruzi , the causative parasite of Chagas heart disease, can infect all nucleated cells of the body and resulted in piRNAs dysregulation which were related to TGFβ and FOS (Rayford et al., 2020).…”

piRNAs as Modulators of Disease Pathogenesis

“…Recently, a group showed that piR-27283 upregulated in human skin tissues infected with Mycobacterium leprae could serve as a potential biomarker of disease. They further implicated piRNAs as possible determinants of macrophage function and nerve regeneration through interactions with IL6R and GAS6 [150].…”