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2020-12-27
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- INI - Artigos de Periódicos [3391]
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MONOCLONAL ANTIBODIES TO HEAT SHOCK PROTEIN 60 ALTER THE PATHOGENESIS OF HISTOPLASMA CAPSULATUM
Autor
Afiliación
Yeshiva University. Albert Einstein College of Medicine. Department of Medicine (Division of Infectious Diseases) & Microbiology and Immunology. New York, NY, USA / Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Micologia. Setor de Imunodiagnóstico. Rio de Janeiro, RJ, Brasil.
Yeshiva University. Albert Einstein College of Medicine. Department of Medicine (Division of Infectious Diseases) & Microbiology and Immunology. New York, NY, USA.
University of Cincinnati. College of Medicine. Cincinnati, OH, USA.
Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Micologia. Setor de Imunodiagnóstico. Rio de Janeiro, RJ, Brasil.
Yeshiva University. Albert Einstein College of Medicine. Department of Medicine (Division of Infectious Diseases) & Microbiology and Immunology. New York, NY, USA.
Yeshiva University. Albert Einstein College of Medicine. Department of Medicine (Division of Infectious Diseases) & Microbiology and Immunology. New York, NY, USA.
University of Cincinnati. College of Medicine. Cincinnati, OH, USA.
Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Micologia. Setor de Imunodiagnóstico. Rio de Janeiro, RJ, Brasil.
Yeshiva University. Albert Einstein College of Medicine. Department of Medicine (Division of Infectious Diseases) & Microbiology and Immunology. New York, NY, USA.
Resumen en ingles
Heat shock proteins with molecular masses of 60 kDa (Hsp60) are widely distributed in nature and are highly conserved immunogenic molecules that can function as molecular chaperones and enhance cellular survival under physiological stress conditions. The fungus Histoplasma capsulatum displays an Hsp60 on its cell surface that is a key target of the cellular immune response during histoplasmosis, and immunization with this
protein is protective. However, the role of humoral responses to Hsp60 has not been fully elucidated. We
generated immunoglobulin G (IgG) isotype monoclonal antibodies (MAbs) to H. capsulatum Hsp60. IgG1 and
IgG2a MAbs significantly prolonged the survival of mice infected with H. capsulatum. An IgG2b MAb was not
protective. The protective MAbs reduced intracellular fungal survival and increased phagolysosomal fusion of
macrophages in vitro. Histological examination of infected mice showed that protective MAbs reduced the
fungal burden and organ damage. Organs of infected animals treated with protective MAbs had significantly
increased levels of interleukin-2 (IL-2), IL-12, and tumor necrosis factor alpha and decreased levels of IL-4 and
IL-10. Hence, IgG1 and IgG2a MAbs to Hsp60 can modify H. capsulatum pathogenesis in part by altering the
intracellular fate of the fungus and inducing the production of Th1-associated cytokines.
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