Hemophagocytic lymphohistiocytosis and macrophage activation syndrome: two rare sides of the same devastating coin

Advances in Rheumatology, Journal Year: 2024, Volume and Issue: 64(1)

Published: April 16, 2024

Abstract Hemophagocytic lymphohistiocytosis (HLH) is a rare genetic hyperinflammatory syndrome that occurs early in life. Macrophage activation (MAS) usually refers to secondary form of HLH associated with autoimmunity, although there are other causes HLH, such as infections and malignancy. In this article, we reviewed the concepts, epidemiology, clinical laboratory features, diagnosis, differential prognosis, treatment MAS. We also presence MAS most common autoimmune diseases affect children. Both severe require prompt diagnosis avoid morbidity mortality.

Language: Английский

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Macrophage Polarisation During Leishmania (Viannia) braziliensis Infection in Mice

Parasite Immunology, Journal Year: 2025, Volume and Issue: 47(1)

Published: Jan. 1, 2025

Leishmania (Viannia) braziliensis causes cutaneous and mucocutaneous leishmaniasis. Macrophages are host cells for parasite replication act as effector against the parasite. The two main macrophage phenotypes (M1 M2) their polarisation states have been implicated in infection despite scarce data on L. (V.) braziliensis. In this study, we investigated temporal spatial distribution predominance of M1 M2 macrophages during Balb/c mice. Animals were infected with promastigotes monitored 25 weeks. Histopathological evaluation footpad lesions, regional lymph nodes, spleen; cellularity; population quantification M1, by flow cytometry performed different tissues. results showed that after either strain lesions small non-ulcerated. dissemination parasites to tissues reinforced characteristic visualisation dermotropicL. proportion was significantly higher than macrophages. Overall, reported here confirm an intracellular parasite, promotes influences phenotype over time, researchers testing therapies based regulation should consider evidence.

Language: Английский

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Profiling Serine Hydrolases in the Leishmania Host‐Pathogen Interactome Using Cell‐Permeable Activity‐Based Fluorophosphonate Probes

ChemBioChem, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Leishmaniasis, a vector‐borne neglected tropical disease, caused by the protozoan parasite Leishmania , is major global public health challenge with millions of new cases annually. Treatment leishmaniasis difficult for many reasons including multiple lifecycle stages, involving both an infective insect vector form, promastigote, and disease‐causing intracellular mammalian host amastigote, increasing drug tolerance that are all linked interplay between host. Activity‐based protein profiling (ABPP) was employed using cell‐permeable fluorophosphonate probes to explore serine hydrolases (SHs) in mexicana subsequent analysis enabled secondary reaction affinity reagent. Importantly, these capable accessing stages disease‐critical intramacrophage amastigote. Probe efficacy combination target engagement accessibility agent. Fourteen SHs, peptidases lipases, were identified L. proteome comparative different life‐stages revealing significant changes SH activity across stages. This ABPP approach provides insights into host–parasite interactome demonstrating SHs function as important virulence factors Z‐Pro‐Prolinal, known prolyl‐oligopeptidase inhibitor, being able reduce infectivity macrophage altering targets.

Language: Английский

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The expression profile of inflammatory microRNAs in Leishmania major infected human macrophages; mining the effects of Leishmania RNA virus

BMC Microbiology, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 2, 2025

Leishmaniasis is a disease caused by the Leishmania parasite. Recent studies suggest critical role for double-stranded RNA virus (LRV) in outcome. MicroRNAs (miRs) are small, non-coding molecules that may also contribute to outcome of infection and pattern disease. This study aimed investigate influence L. major infected with LRV2 + on expression profile microRNAs compared LRV2-. Samples were collected from cutaneous leishmaniasis (CL) patients leishmaniasis-endemic area Iran. species determined using PCR (kDNA gene), presence was identified semi-nested (RdRp gene). The miRs (miR-155, miR-146b, miR-133a) through quantitative real-time analysis human monocytes cell line (THP-1) both LRV2- isolates during 0, 12, 24, 36 h post-co-infection. miR-155 showed significant decrease isolate at zero hours, but exhibited upregulation post-infection control group. miR-146b upregulated group zero, post-infection. Conversely, miR-133a increases 12 group, it downregulated 24 In this study, differences observed profiles miR-155, about LRV2. Our data potential determinative these pathogenesis CL.

Language: Английский

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An overview of host immune responses against Leishmania spp. infections

Human Molecular Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: April 27, 2025

Abstract Leishmania spp. infections pose a significant global health challenge, affecting approximately 1 billion people across more than 88 endemic countries. This unicellular, obligate intracellular parasite causes spectrum of diseases, ranging from localized cutaneous lesions to systemic visceral infections. Despite advancements in modern medicine and increased understanding the parasite’s etiology associated treatment options remain limited pentavalent antimonials, liposomal amphotericin B, miltefosine. A deeper interactions between immune non-immune cells involved clearance could uncover novel therapeutic strategies for this debilitating disease. review highlights recent progress elucidating how various cell types contribute regulation resolution

Language: Английский

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Altered purinergic P2X7 and A2B receptors signaling limits macrophage-mediated host defense in schistosomiasis

Biomedical Journal, Journal Year: 2024, Volume and Issue: 47(6), P. 100713 - 100713

Published: March 3, 2024

The occurrence of co-infections during schistosomiasis, a neglected tropical disease, with other parasites have been reported suggesting an impaired host immune defense. Macrophage purinergic P2X7 receptor (P2X7R) plays important role against intracellular pathogens. Therefore, we investigated the P2X7R-mediated phagocytosis and killing capacity Leishmania amazonensis by macrophages schistosomiasis in vitro vivo.

Language: Английский

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Chlorpyrifos-induced suppression of the antioxidative defense system leads to cytotoxicity and genotoxicity in macrophages

Environmental Toxicology and Pharmacology, Journal Year: 2024, Volume and Issue: 108, P. 104468 - 104468

Published: May 15, 2024

Chlorpyrifos, widely used for pest control, is known to have various harmful effects, although its toxic effects in macrophages and the mechanisms underlying toxicity remain unclear. The present study investigated of chlorypyrifos a macrophage cell line. Here, we found that chlorpyrifos induced cytotoxicity genotoxicity RAW264.7 macrophages. Moreover, intracellular ROS production, subsequently leading lipid peroxidation. Chlorpyrifos reduced activation antioxidative enzymes including superoxide dismutase, catalase, glutathione peroxidase. upregulated HO-1 expression activated Keap1-Nrf2 pathway, as indicated by enhanced Nrf2 phosphorylation Keap1 degradation. exerted on following dose-dependent manner: cytotoxicity, genotoxicity, peroxidation, enzyme activity reduction, expression, phosphorylation, Notably, N-acetyl-L-cysteine successfully inhibited chlorpyrifos-induced generation, genotoxicity. Thus, may induce promoting production suppressing defense system

Language: Английский

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Diagnostic challenges in cutaneous leishmaniasis due to atypical Leishmania infantum: pathologists’ insights from re-emergence zones

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Sept. 12, 2024

Leishmaniasis, a parasitic infection affecting both humans and animals, is increasingly spreading across Mediterranean European regions, largely driven by human migration environmental changes. In countries like Türkiye Europe, which have seen large influxes of migrants, the incidence cutaneous leishmaniasis (CL) rising, with cases now appearing in cities where disease was previously undocumented. these non-endemic areas, physicians unfamiliar characteristic lesions may misdiagnose CL, particularly only manifestations. This study aims to evaluate impact re-emerging CL on routine diagnostic practices pathologists Türkiye, retrospectively reviewing cases.

Language: Английский

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Leishmania LPG interacts with LRR5/LRR6 of macrophage TLR4 for parasite invasion and impairs the macrophage functions

Pathogens and Disease, Journal Year: 2023, Volume and Issue: 81

Published: Jan. 1, 2023

Visceral leishmaniasis (VL) is a severe form of leishmaniasis, primarily affecting the poor in developing countries. Although several studies have highlighted importance toll-like receptors (TLRs) pathophysiology role specific TLRs and their binding partners involved Leishmania donovani uptake are still elusive. To investigate mechanism L. entry inside macrophages, we found that parasite lipophosphoglycan (LPG) interacted with macrophage TLR4, leading to without any significant alteration cell viability. Increased numbers within macrophages markedly inhibited lipopolysachharide-induced pro-inflammatory cytokines gene expression. Silencing macrophage-TLR4, or inhibition parasite-LPG, significantly stemmed infection macrophages. Interestingly, observed enhancement migration, generation reactive oxygen species (ROS) parasite-infected TLR4-silenced whereas TLR4-overexpressed exhibited notable reduction migration ROS generation. Moreover, mutations leucine-rich repeats (LRRs), particularly LRR5 LRR6, prevented TLR4 interaction LPG, thus inhibiting cellular entry. All these results suggest LPG recognition by LRR6 macrophage-TLR4 facilitated entry, impaired functions. Therefore, targeting LRR5/LRR6 interactions could provide novel option prevent VL.

Language: Английский

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Gene Expression Profiling of Classically Activated Macrophages in Leishmania infantum Infection: Response to Metabolic Pre-Stimulus with Itaconic Acid

Tropical Medicine and Infectious Disease, Journal Year: 2023, Volume and Issue: 8(5), P. 264 - 264

Published: May 3, 2023

Leishmania infection of phagocytic cells, such as macrophages, induces the differentiation infected cells into different phenotypes according to their surrounding microenvironments. The classical activation macrophages involves metabolic reprogramming, in which several metabolites succinate, fumarate and itaconate are accumulated. immunoregulatory functions context were investigated this paper. Ex vivo bone marrow-derived differentiated classically activated through IFNG with infantum. A high-throughput real-time qPCR experiment was designed for analyses 223 genes involved immune response metabolism. transcriptional profile revealed enrichment pathways upregulation Cxcl9, Irf1, Acod1, Il12b, Il12rb1, Nos2 or Stat1. In vitro pre-stimulation induced a loss parasite control related local acute inflammatory response. Our results reveal that accumulation dampened macrophage antiparasitic activity, is reflected by differential expression Icosl Mki67 genes. possibility inducing parasite-killing responses host reprograming an interesting approach treatment infections will undoubtedly attract increasing attention coming years.

Language: Английский

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