Host membrane glycosphingolipids and lipid microdomains facilitate Histoplasma capsulatum internalisation by macrophages.

Autor:	Guimarães AJ; Department of Microbiology and Parasitology, Biomedical Institute, Fluminense Federal University, Rio de Janeiro, Brazil.; Departments of Medicine (Division of Infectious Diseases) and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York., de Cerqueira MD; Department of General Microbiology, Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Zamith-Miranda D; Department of General Microbiology, Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Lopez PH; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland., Rodrigues ML; Department of General Microbiology, Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.; Instituto Carlos Chagas, Fundação Oswaldo Cruz (Fiocruz), Curitiba, Brazil., Pontes B; LPO-COPEA, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Viana NB; LPO-COPEA, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.; LPO-COPEA, Institute of Physics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., DeLeon-Rodriguez CM; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland., Rossi DCP; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland., Casadevall A; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland., Gomes AMO; Program of Structural Biology, Institute of Medical Biochemistry Leopoldo de Meis and National Institute of Science and Technology of Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Martinez LR; Biological Sciences, The University of Texas at El Paso, El Paso, Texas., Schnaar RL; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland., Nosanchuk JD; Departments of Medicine (Division of Infectious Diseases) and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York., Nimrichter L; Department of General Microbiology, Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Jazyk:	angličtina
Zdroj:	Cellular microbiology [Cell Microbiol] 2019 Mar; Vol. 21 (3), pp. e12976. Date of Electronic Publication: 2018 Dec 07.
DOI:	10.1111/cmi.12976
Abstrakt:	Recognition and internalisation of intracellular pathogens by host cells is a multifactorial process, involving both stable and transient interactions. The plasticity of the host cell plasma membrane is fundamental in this infectious process. Here, the participation of macrophage lipid microdomains during adhesion and internalisation of the fungal pathogen Histoplasma capsulatum (Hc) was investigated. An increase in membrane lateral organisation, which is a characteristic of lipid microdomains, was observed during the first steps of Hc-macrophage interaction. Cholesterol enrichment in macrophage membranes around Hc contact regions and reduced levels of Hc-macrophage association after cholesterol removal also suggested the participation of lipid microdomains during Hc-macrophage interaction. Using optical tweezers to study cell-to-cell interactions, we showed that cholesterol depletion increased the time required for Hc adhesion. Additionally, fungal internalisation was significantly reduced under these conditions. Moreover, macrophages treated with the ceramide-glucosyltransferase inhibitor (P4r) and macrophages with altered ganglioside synthesis (from B4galnt1 -/- mice) showed a deficient ability to interact with Hc. Coincubation of oligo-GM1 and treatment with Cholera toxin Subunit B, which recognises the ganglioside GM1, also reduced Hc association. Although purified GM1 did not alter Hc binding, treatment with P4 significantly increased the time required for Hc binding to macrophages. The content of CD18 was displaced from lipid microdomains in B4galnt1 -/- macrophages. In addition, macrophages with reduced CD18 expression (CD18 low ) were associated with Hc at levels similar to wild-type cells. Finally, CD11b and CD18 colocalised with GM1 during Hc-macrophage interaction. Our results indicate that lipid rafts and particularly complex gangliosides that reside in lipid rafts stabilise Hc-macrophage adhesion and mediate efficient internalisation during histoplasmosis. (© 2018 John Wiley & Sons Ltd.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu