Monoclonal Antibodies to Heat Shock Protein 60 Alter the Pathogenesis ofHistoplasma capsulatum
- 1 April 2009
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 77 (4), 1357-1367
- https://doi.org/10.1128/iai.01443-08
Abstract
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 fungusHistoplasma capsulatumdisplays 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) toH. capsulatumHsp60. IgG1 and IgG2a MAbs significantly prolonged the survival of mice infected withH. 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 modifyH. capsulatumpathogenesis in part by altering the intracellular fate of the fungus and inducing the production of Th1-associated cytokines.Keywords
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