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Glucuronoxylomannan-mediated interaction of Cryptococcus neoformans with human alveolar cells results in fungal internalization and host cell damage
Authors:Barbosa Fabiane M  Fonseca Fernanda L  Holandino Carla  Alviano Celuta S  Nimrichter Leonardo  Rodrigues Marcio L
Institution:1. Laboratório de Estudos Integrados em Bioquímica Microbiana, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Cidade Universitária, CCS, Bloco I, Ilha do Fundão, Rio de Janeiro, RJ 21941590, Brazil;2. Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, RJ 21941590, Brazil;3. Laboratório de Estruturas de Superfície de Microrganismos, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, RJ 21941590, Brazil;4. Disciplina de Biologia Celular, Universidade Federal de São Paulo, São Paulo, SP 04023-062, Brazil;1. Department of Health Sciences, University of Milan, Polo Universitario San Paolo, Via Di Rudinì 8 – Blocco C, 8° piano, 20142 Milano, Italy;2. Department of Diagnostics, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy;3. Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125 Modena, Italy;1. Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany,;2. Center for Sepsis Control and Care, University Hospital Jena, Germany,;3. Institute of Medical Microbiology, Medical School Hannover, Germany,;4. Institute for Transfusion Medicine, Medical Faculty, Friedrich Schiller University Jena Germany,;5. Microbial Immunology Group, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany,;6. University of Würzburg, Institute for Virology and Immunobiology, Würzburg, Germany,;7. Friedrich Schiller University, Jena, Germany,;1. Laboratório de Bioquímica e Microbiologia Aplicada, Instituto de Ciência e Tecnologia de Alimentos, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil;2. Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA;3. Department of Agricultural and Food Sciences, Università di Bologna, Bologna, Italy;1. Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India;2. National Institute of Plant Genome Research, New Delhi 110067, India
Abstract:Infection by Cryptococcus neoformans begins with inhalation of infectious propagules. Fungi reach the lung tissue and interact with epithelial cells in a crucial but poorly understood process. In this study, the interaction of C. neoformans with the human alveolar epithelial cell lineage A549 was investigated, focusing on the relevance of the capsular polysaccharide in this process. The association of encapsulated strains with A549 cells was significantly inhibited by a monoclonal antibody to glucuronoxylomannan (GXM), a major component of the cryptococcal capsule. A purified preparation of GXM produced similar results, suggesting the occurrence of surface receptors for this polysaccharide on the surface of alveolar cells. A549 cells were in fact able to bind soluble GXM, as confirmed by indirect immunofluorescence analysis using the anti-polysaccharide antibody. C. neoformans is internalized after GXM-mediated interaction with A549 cells in a process that culminates with death of host cells. Our results suggest that C. neoformans can use GXM for attachment to alveolar epithelia, allowing the fungus to reach the intracellular environment and damage host cells through still uncharacterized mechanisms.
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