Intracellular parasites are known to persist lifelong in mammalian hosts after the clinical cure of the disease, but the mechanisms of persistence are poorly understood. Here, we show by confocal laser microscopy that in the draining lymph nodes of mice that had healed a cutaneous infection with Leishmania major, 40% of the persisting parasites were associated with fibroblasts forming the reticular meshwork of the lymph nodes. In vitro, both promastigotes and amastigotes of L. major infected primary skin or lymph node fibroblasts. Compared with macrophages, cytokine-activated fibroblasts had a reduced ability to express type 2 nitric oxide synthase and to kill intracellular L. major. These data identify fibroblasts as an important host cell for Leishmania during the chronic phase of infection and suggest that they might serve as safe targets for the parasites in clinically latent disease.
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http://dx.doi.org/10.1084/jem.191.12.2121 | DOI Listing |
Microbiol Spectr
January 2025
Instituto de Biociências, Universidade Estadual Paulista (UNESP), Botucatu, Brazil.
is a pathogen that causes sporadic cases and outbreaks of diarrhea. The main virulence feature of this bacterium is the attaching and effacing (AE) lesion formation on infected intestinal epithelial cells, which is characterized by the formation of pedestal-like structures that are rich in F-actin. The Brazilian 1551-2 strain can recruit F-actin using both the Nck-dependent and the Nck-independent pathways, the latter of which uses an adaptor protein named Tir-cytoskeleton coupling protein (TccP/EspF).
View Article and Find Full Text PDFCytokine
January 2025
Department of Molecular Biology and Bioinformatics, Tripura University, Agartala, India. Electronic address:
Transforming growth factor-beta (TGF-β), displaying a dual role in immunosuppression and pathogenesis, has emerged as a key regulator of anti-leishmanial immune responses. In Leishmania infections, TGF-β drives immune deviation by enhancing regulatory T-cell (T-reg) differentiation and inhibiting macrophage activation, suppressing critical antiparasitic responses. This cytokine simultaneously promotes fibroblast proliferation, extracellular matrix production, and fibrosis in infected tissues, which aids in wound healing but impedes immune cell infiltration, particularly in visceral leishmaniasis, where splenic disorganization and compromised immune access are notable.
View Article and Find Full Text PDFUnlabelled: The gut microbiota influences systemic immunity and the function of distal tissues, including the brain, liver, skin, lung, and muscle. However, the role of the gut microbiota in the foreign body response (FBR) and fibrosis around medical implants is largely unexplored. To investigate this connection, we perturbed the homeostasis of the murine gut microbiota via enterotoxigenic (ETBF) infection and implanted the synthetic polymer polycaprolactone (PCL) into a distal muscle injury.
View Article and Find Full Text PDFPharmaceuticals (Basel)
December 2024
Department of Biochemistry, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico.
Infection with the protozoan parasite causes human Chagas disease. Benznidazole (BNZ) and nifurtimox are the current drugs for the treatment; however, they induce severe adverse side effects in patients; therefore, there is a need to improve the treatment effectiveness and efficiency of these drugs for its safer use. : Glyburide, glipizide, and gliquidone, hypoglycemic drugs for diabetes treatment, were previously predicted to bind to dihydrofolate reductase-thymidylate synthase from by in silico docking analysis; they also showed antiproliferative effects against epimastigotes, the stage of the insect vector.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Head and Neck Oncology Group, Centre for Host Microbiome Interaction, King's College London, Hodgkin Building, London SE1 1UL, UK.
Background: Cancer-associated fibroblasts have been reported to play a central role in driving cancer progression, promoting metastasis, and conferring resistance to therapy in HNSCC.
Methods: Indirect and direct co-culture models of HPV-positive and HPV-negative HNSCC cells with fibroblasts were developed to study the effect of fibroblasts on cancer cells. ELISA was used to measure IL-6 secretion in these models.
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