Monoclonal antibodies to heat shock protein 60 alter the pathogenesis of Histoplasma capsulatum

dc.creatorGuimarães, Allan J.
dc.creatorFrases, Susana
dc.creatorGomez, Francisco J.
dc.creatorZancopé-Oliveira, Rosely M.
dc.creatorNosanchuk, Joshua D.
dc.date2019-12-27T12:24:45Z
dc.date2019-12-27T12:24:45Z
dc.date2009
dc.date.accessioned2023-09-26T20:28:29Z
dc.date.available2023-09-26T20:28:29Z
dc.identifierGUIMARÃES, Allan J. et al. Monoclonal antibodies to heat shock protein 60 alter the pathogenesis of Histoplasma capsulatum. Infection and Immunity, v. 77, n. 4, p. 1357-1367, Apr. 2009.
dc.identifier0019-9567
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/38880
dc.identifier10.1128/IAI.01443-08
dc.identifier1098-5522
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8857706
dc.descriptionHeat 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.
dc.description2020-12-27
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Society for Microbiology
dc.rightsopen access
dc.subjectHistoplasma capsulatum
dc.subjectMonoclonal antibodies
dc.subjectHeat shock proteins
dc.titleMonoclonal antibodies to heat shock protein 60 alter the pathogenesis of Histoplasma capsulatum
dc.typeArticle


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