Work

Fh15 modulates in vitro phagocytosis and cytokine responses in LPS-stimulated bone marrow-derived macrophages: implication for sepsis therapy 3734

Year: 2025

Type: article

Abstract: Description Excretory-secretory products from F. hepatica influence phagocytic cells, altering cytokine production and immune responses. Fh15 suppresses the NF-κB pathway, reducing pro-inflammatory cytokines like TNF-α and IL-1β, typically elevated during sepsis. Additionally, chronic F. hepatica infections in sheep, are associated with increased IL-10 levels, a regulatory cytokine that helps parasite immune evasion. These findings highlight Fh15 as a potential therapeutic agent to control inflammation in sepsis and other inflammatory diseases. To determine whether Fh15 can modify the ability of macrophages to phagocytise bacteria, we performed an in vitro phagocytosis assay. Bone marrow-derived macrophages from naïve mice were isolated and treated with LPS, Fh15 or both. We also quantify the expression of CD36, a scavenger receptor that resulted upregulated in a previous proteomic analysis and its engagement is necessary for effective phagocytosis of apoptotic cells. Finally, we analyze gene expression of TNF-α and IL-10, inflammatory and regulatory cytokines, using RT-qPCR. Fh15 suppressed phagocytosis in LPS-treated cells, reduce TNF-α gene expression, and increase IL-10 gene expression in cells that received Fh15 + LPS. These results suggest Fh15 regulates macrophage dynamics, potentially regulating immune inflammatory responses. By mitigating excessive inflammation and modulating phagocytosis, Fh15 holds promise as a therapeutic agent for sepsis and related inflammatory conditions. Funding Sources This work was supported by NIAID/NIH grant number SC1AI155439-01 and 2023 AAI Careers in Immunology Fellowship Program. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1499

Authors: Albersy Armina-Rodriguez, Carlimar Ocasio-Malavé, María Del Mar Figueroa-Gispert, Alejandro Escalante-Castaneda, Ana M. Espino, Riseilly Ramos Nieves

Institutions: University of Puerto Rico, Medical Sciences Campus, University of Puerto Rico at Río Piedras

Language: English

Topic: Parasites and Host Interactions

Subfield: Parasitology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze