In a groundbreaking study published recently in Acta Parasitologica, researchers have unveiled critical differences in microRNA expression between acute and chronic forms of cutaneous leishmaniasis, a parasitic disease that continues to impose a significant global health burden. The study, spearheaded by Hamedanipour, Khosravany, Mirabedini, and colleagues, delves deeply into the molecular underpinnings that distinguish the two clinical manifestations, focusing particularly on miR-155, miR-133a, and miR-146b levels in patient serum samples. This research not only opens new pathways for diagnostics but also suggests novel therapeutic interventions targeting these microRNAs.
Cutaneous leishmaniasis (CL) is caused by several species of the protozoan parasite Leishmania, transmitted by sandfly bites, and presents largely as skin lesions that can be either self-healing or progress into chronic, debilitating wounds. The clinical heterogeneity of CL has long puzzled clinicians and researchers alike, making it imperative to identify biomarkers that could predict disease course and treatment outcomes. Central to this quest are microRNAs (miRNAs)—small, non-coding RNA molecules that regulate gene expression post-transcriptionally and play vital roles in immune system modulation and pathogen-host interactions.
The study’s fundamental question targets the expression patterns of three microRNAs: miR-155, miR-133a, and miR-146b, each known from prior studies to be involved in various inflammatory and immune responses. The investigators hypothesized that divergent miRNA profiles in acute versus chronic CL could reflect the differential host immune reactions determining disease resolution or persistence. To address this, serum samples were collected from patients clinically diagnosed with either acute or chronic CL, allowing the quantitative assessment of miRNA levels via advanced molecular techniques.
Their findings revealed a significant upregulation of miR-155 and miR-146b in patients with acute CL, while miR-133a exhibited a contrasting downregulated pattern relative to chronic cases. miR-155 is well-documented for its role in promoting Th1-type immune responses, which are critical for controlling Leishmania parasites. The elevated miR-155 in acute cases likely corresponds with active immune engagement attempting to eradicate the pathogen, an observation that aligns with previous reports linking this miRNA to inflammatory macrophage activation and parasite clearance.
Conversely, the chronic form showed increased suppression of miR-155 alongside the relative upregulation of miR-133a, suggesting a subdued immune activation that may allow parasite persistence and lesion chronicity. miR-133a, traditionally associated with muscle differentiation and repair pathways, is increasingly recognized for its immunomodulatory functions, possibly contributing to tissue remodeling or immune evasion in chronic infections. The role of miR-146b, often characterized as a negative regulator of inflammation, emerged as complex; its overexpression in acute cases may represent a feedback mechanism restraining excessive immune damage.
Technically, the study employed quantitative real-time PCR (qRT-PCR) to determine serum miRNA levels, ensuring high sensitivity and reproducibility. Serum was chosen as a minimally invasive sample type reflecting systemic molecular changes during infection. The researchers also validated the integrity of the miRNAs against controls, confirming that observed differences were not artifacts but truly representative of underlying disease processes. Such methodological rigor strengthens confidence in the utility of these miRNAs as biomarkers.
Understanding miRNA dynamics in leishmaniasis holds profound implications. From a diagnostic perspective, the distinct expression patterns could enable the development of rapid blood-based tests distinguishing acute from chronic forms, a critical need in clinical settings where lesion appearance alone is insufficient for prognosis. Moreover, these miRNAs could serve as predictive markers for treatment responsiveness, guiding personalized medicine approaches that may enhance patient outcomes and reduce unnecessary drug exposure.
Therapeutically, targeting miRNAs presents a novel frontier. For example, enhancing miR-155 activity or modulating miR-133a could reinvigorate host immune responses and promote lesion healing in chronic CL cases. This strategy circumvents conventional chemotherapeutic paradigms, which often suffer from toxicity, high costs, and emerging drug resistance. Instead, miRNA-based therapeutics could offer precision interventions with potentially fewer side effects by fine-tuning immune pathways impaired during infection.
The study also contributes to broader infectious disease biology by illustrating how pathogens manipulate host miRNA networks to their advantage. The differential regulation observed underscores a battle at the molecular level between host defenses and parasitic adaptation. Recognizing such interactions expands our understanding beyond simple parasite killing, highlighting the importance of immune regulation and tissue homeostasis in disease outcomes.
Intriguingly, the research touches on the systemic nature of CL—typically considered localized to the skin—by demonstrating that serum miRNAs reflect local immune events. This suggests that circulating miRNAs could mirror not only local infection sites but also systemic immune alterations, making them valuable as non-invasive biomarkers in endemic regions. Further studies could elucidate whether these miRNAs correlate with other clinical parameters such as lesion size, duration, or patient immune status.
While this study marks a significant advance, it also raises new questions. The exact mechanistic roles of miR-133a and miR-146b in leishmanial pathology remain to be fully elucidated through in vitro and in vivo functional studies. Additionally, it will be critical to investigate whether these miRNA signatures hold across diverse Leishmania strains and varied host genetic backgrounds, ensuring broad applicability in global health contexts.
Future research directions proposed by the authors include integrating miRNA profiling with transcriptomic and proteomic data to construct comprehensive molecular networks affected during CL. Such multi-omics approaches could identify additional regulatory nodes and potential drug targets. Moreover, longitudinal studies following patients through treatment could validate whether miRNA levels dynamically correlate with therapeutic success or relapse.
This pioneering research thus propels a paradigm shift in how cutaneous leishmaniasis can be understood and managed. By shining a spotlight on miRNAs—once considered mere molecular bystanders—it reveals their centrality in orchestrating immune responses that dictate disease trajectories. These insights not only enrich parasitology and immunology literature but also pave the way for translational breakthroughs with real-world impact.
As cutaneous leishmaniasis continues to affect millions worldwide, particularly in resource-limited settings, innovations like miRNA-based diagnostics and therapies offer hope for improved control measures. The elegant molecular work embodied in this study exemplifies how dissecting host-pathogen interactions at the microRNA level can decode complex diseases and facilitate the development of next-generation medical interventions tailored to patient needs.
In summary, Hamedanipour and colleagues’ investigation into miR-155, miR-133a, and miR-146b expression patterns provides compelling evidence that these small molecules serve as crucial regulators and potential biomarkers differentiating acute and chronic cutaneous leishmaniasis. Their work underscores the intricate molecular crosstalk governing disease progression and opens exciting vistas for innovative diagnostic and therapeutic strategies aimed at mitigating the global burden of leishmaniasis.
Subject of Research: Investigation of microRNA expression patterns—specifically miR-155, miR-133a, and miR-146b—in serum samples from patients with acute and chronic cutaneous leishmaniasis to understand molecular differences influencing disease forms.
Article Title: Investigation of the Expression Levels of miR-155, miR-133a, and miR-146b in the Serum of Acute and Chronic Forms of Cutaneous Leishmaniasis.
Article References:
Hamedanipour, M., Khosravany, Z., Mirabedini, Z., et al. Investigation of the Expression Levels of miR-155, miR-133a, and miR-146b in the Serum of Acute and Chronic Forms of Cutaneous Leishmaniasis. Acta Parasit. 70, 185 (2025). https://doi.org/10.1007/s11686-025-01123-x
Image Credits: AI Generated
