Sustained neutrophil infiltration and bacterial grain morphology underlie chronic mycetoma pathology in a murine model

Objective(s): This study aimed to characterize the progression of chronic mycetoma caused by Nocardia brasiliensis in a BALB/c murine model, focusing on the interplay between host cellular immune responses, bacterial burden, and histopathological evolution.Materials and Methods: BALB/c mice were ino...

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Main Authors: Maria Ruiz-de la Cruz, Anna Vazquez-Marmolejo, Manuel Mejia-Torres, Maria Castro-Corona, Mario Salinas-Carmona
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2025-09-01
Series:Iranian Journal of Basic Medical Sciences
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Online Access:https://ijbms.mums.ac.ir/article_26172_ebd96336d0e3fa0000f67998ee2771e6.pdf
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author Maria Ruiz-de la Cruz
Anna Vazquez-Marmolejo
Manuel Mejia-Torres
Maria Castro-Corona
Mario Salinas-Carmona
author_facet Maria Ruiz-de la Cruz
Anna Vazquez-Marmolejo
Manuel Mejia-Torres
Maria Castro-Corona
Mario Salinas-Carmona
author_sort Maria Ruiz-de la Cruz
collection DOAJ
description Objective(s): This study aimed to characterize the progression of chronic mycetoma caused by Nocardia brasiliensis in a BALB/c murine model, focusing on the interplay between host cellular immune responses, bacterial burden, and histopathological evolution.Materials and Methods: BALB/c mice were inoculated with N. brasiliensis in the left hind footpad to establish the mycetoma model. The mice were divided into four experimental groups: 0, 70, 100, and 365 days post-infection (dpi). Lesion volume was assessed throughout the course of infection. At the defined time points, bacterial load (serial dilution method), percentages of immune cell populations (flow cytometry), serum cytokines (interleukins IL-6, IL-10, and IL-12p70, monocyte chemoattractant protein-1 (MCP-1), interferon-gamma (IFN-γ), and tumor necrosis factor (TNF)) via cytometric bead array (CBA), as well as histopathology and bacterial grain morphology (H&E staining), were evaluated.Results: Chronic mycetoma progression revealed stable bacterial burden and lesion volume stabilization after 70 dpi through 365 dpi. Systemic expansion of CD4+ T cells in the spleen and sustained neutrophil dominance (>90% infiltration) characterized chronic lesions. Progressive tissue necrosis and panniculitis, undetectable by external lesion size, emerged histologically. Serum IL-6 levels surged during chronicity, suggesting a Th17 polarization, contrasting with declining MCP-1. Bacterial grains transitioned from club-shaped to circular over time, suggesting structural grain remodeling.Conclusion: In chronic experimental mycetoma, the cell response is mainly characterized by neutrophil infiltration, an altered CD4+ T cell response, and dysregulated cytokine production. The shape of bacterial grains continues to change, and the bacterial load remains constant.
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2008-3874
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publishDate 2025-09-01
publisher Mashhad University of Medical Sciences
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spelling doaj-art-b5621d3e5101418ab7baaa7aaae910422025-08-20T03:56:42ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742025-09-012891268127810.22038/ijbms.2025.87349.1887526172Sustained neutrophil infiltration and bacterial grain morphology underlie chronic mycetoma pathology in a murine modelMaria Ruiz-de la Cruz0Anna Vazquez-Marmolejo1Manuel Mejia-Torres2Maria Castro-Corona3Mario Salinas-Carmona4Department of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, MexicoDepartment of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, MexicoDepartment of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, MexicoDepartment of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, MexicoDepartment of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, MexicoObjective(s): This study aimed to characterize the progression of chronic mycetoma caused by Nocardia brasiliensis in a BALB/c murine model, focusing on the interplay between host cellular immune responses, bacterial burden, and histopathological evolution.Materials and Methods: BALB/c mice were inoculated with N. brasiliensis in the left hind footpad to establish the mycetoma model. The mice were divided into four experimental groups: 0, 70, 100, and 365 days post-infection (dpi). Lesion volume was assessed throughout the course of infection. At the defined time points, bacterial load (serial dilution method), percentages of immune cell populations (flow cytometry), serum cytokines (interleukins IL-6, IL-10, and IL-12p70, monocyte chemoattractant protein-1 (MCP-1), interferon-gamma (IFN-γ), and tumor necrosis factor (TNF)) via cytometric bead array (CBA), as well as histopathology and bacterial grain morphology (H&E staining), were evaluated.Results: Chronic mycetoma progression revealed stable bacterial burden and lesion volume stabilization after 70 dpi through 365 dpi. Systemic expansion of CD4+ T cells in the spleen and sustained neutrophil dominance (>90% infiltration) characterized chronic lesions. Progressive tissue necrosis and panniculitis, undetectable by external lesion size, emerged histologically. Serum IL-6 levels surged during chronicity, suggesting a Th17 polarization, contrasting with declining MCP-1. Bacterial grains transitioned from club-shaped to circular over time, suggesting structural grain remodeling.Conclusion: In chronic experimental mycetoma, the cell response is mainly characterized by neutrophil infiltration, an altered CD4+ T cell response, and dysregulated cytokine production. The shape of bacterial grains continues to change, and the bacterial load remains constant.https://ijbms.mums.ac.ir/article_26172_ebd96336d0e3fa0000f67998ee2771e6.pdfanimal disease modelsgranulomahost-pathogen interactionsimmune dysregulationneutrophil infiltration nocardia infections
spellingShingle Maria Ruiz-de la Cruz
Anna Vazquez-Marmolejo
Manuel Mejia-Torres
Maria Castro-Corona
Mario Salinas-Carmona
Sustained neutrophil infiltration and bacterial grain morphology underlie chronic mycetoma pathology in a murine model
Iranian Journal of Basic Medical Sciences
animal disease models
granuloma
host-pathogen interactions
immune dysregulation
neutrophil infiltration nocardia infections
title Sustained neutrophil infiltration and bacterial grain morphology underlie chronic mycetoma pathology in a murine model
title_full Sustained neutrophil infiltration and bacterial grain morphology underlie chronic mycetoma pathology in a murine model
title_fullStr Sustained neutrophil infiltration and bacterial grain morphology underlie chronic mycetoma pathology in a murine model
title_full_unstemmed Sustained neutrophil infiltration and bacterial grain morphology underlie chronic mycetoma pathology in a murine model
title_short Sustained neutrophil infiltration and bacterial grain morphology underlie chronic mycetoma pathology in a murine model
title_sort sustained neutrophil infiltration and bacterial grain morphology underlie chronic mycetoma pathology in a murine model
topic animal disease models
granuloma
host-pathogen interactions
immune dysregulation
neutrophil infiltration nocardia infections
url https://ijbms.mums.ac.ir/article_26172_ebd96336d0e3fa0000f67998ee2771e6.pdf
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