cell-migration-cell-adhesion-assays-to-investigate-leishmania-host

Cell Migration and Cell Adhesion Assays to Investigate <em>Leishmania</em>-Host Cell Interaction

Leishmania is an intracellular protozoan parasite that causes a broad spectrum of clinical manifestations, ranging from self-resolving localized cutaneous ...

Gonçalo Moniz Institute

Localized cutaneous leishmaniasis (LCL) is a chronic disease characterized by ulcerated skin lesion(s) and uncontrolled inflammation. The mechanisms underlying the pathogenesis of LCL are not completely understood, and little is known about posttranscriptional regulation during LCL. MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression and can be implicated in the pathogenesis of LCL. We investigated the involvement of miRNAs and their targets genes in human LCL using publicly available transcriptome data sets followed by  validation. Initial analysis highlighted that miRNA expression is altered during LCL, as patients clustered separately from controls. Joint analysis identified eight high confidence miRNAs that had altered expression (-1.5 ≤ fold change ≥ 1.5;  < 0.05) between cutaneous ulcers and uninfected skin. We found that the expression of miR-193b and miR-671 are greatly associated with their target genes, CD40 and TNFR, indicating the important role of these miRNAs in the expression of genes related to the inflammatory response observed in LCL. In addition, network analysis revealed that miR-193b, miR-671, and  correlate only in patients who show faster wound healing (up to 59 days) and not in patients who require longer cure times (more than 60 days). Given that these miRNAs are associated with control of inflammation and healing time, our findings reveal that they might influence the pathogenesis and prognosis of LCL.

Integrated Analysis Reveals That miR-193b, miR-671, and TREM-1 Correlate With a Good Response to Treatment of Human Localized Cutaneous Leishmaniasis Caused by .

Dendritic cells (DC) are a diverse group of leukocytes responsible for bridging innate and adaptive immunity. Despite their functional versatility, DCs exist primarily in two basic functional states: immature and mature. A large body of evidence suggests that upon interactions with pathogens, DCs undergo intricate cellular processes that culminate in their activation, which is paramount to the orchestration of effective immune responses against a parasites. Herein we offer a concise review of the emerging hallmarks of DCs activation in leishmaniasis as well as a comprehensive discussion of the following underlying molecular events: DC- interaction, antigen uptake, costimulatory molecule expression, parasite ability to affect DC migration, antigen presentation, metabolic reprogramming, and epigenetic alterations.

Molecular Aspects of Dendritic Cell Activation in Leishmaniasis: An Immunobiological View.

The initial production of inflammatory mediators dictates host defense as well as tissue injury. Inflammasome activation is a constituent of the inflammatory response by recognizing pathogen and host-derived products and eliciting the production of IL-1β and IL-18 in addition to inducing a type of inflammatory cell death termed "pyroptosis." Leukotriene B (LTB) is a lipid mediator produced quickly (seconds to minutes) by phagocytes and induces chemotaxis, increases cytokine/chemokine production, and enhances antimicrobial effector functions. Whether LTB directly activates the inflammasome remains to be determined. Our data show that endogenously produced LTB is required for the expression of pro-IL-1β and enhances inflammasome assembly in vivo and in vitro. Furthermore, LTB-mediated Bruton's tyrosine kinase (BTK) activation is required for inflammasome assembly in vivo as well for IL-1β-enhanced skin host defense. Together, these data unveil a new role for LTB in enhancing the expression and assembly of inflammasome components and suggest that while blocking LTB actions could be a promising therapeutic strategy to prevent inflammasome-mediated diseases, exogenous LTB can be used as an adjuvant to boost inflammasome-dependent host defense.

Article	Year
Integrated Analysis Reveals That miR-193b, miR-671, and TREM-1 Correlate With a Good Response to Treatment of Human Localized Cutaneous Leishmaniasis Caused by . Frontiers in immunology\| PubMed ID: 29670621	2018
Molecular Aspects of Dendritic Cell Activation in Leishmaniasis: An Immunobiological View. Frontiers in immunology\| PubMed ID: 30873156	2019
Leukotriene B licenses inflammasome activation to enhance skin host defense. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 33184178	2020

Natalia Machado Tavares

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