Heat shock protein 70 (hsp70) as a major target of the antibody response in patients with pulmonary cryptococcosis

Abstract

Cryptococcus neoformans causes infection in individuals with defective T cell function, such as AIDS, as well as without underlying disease. It has been suggested that humoral as well as cellular immunity might play an important role in the immune response to C. neoformans infection. We have recently shown, using immunoblotting, that the 70-kD hsp family of C. neoformans was the major target molecule of the humoral response in murine pulmonary cryptococcosis. In this study we also used immunoblotting to define the antibody responses in the sera of 24 patients with pulmonary cryptococcosis: 21 proven and three suspected diagnoses. Anti-C. neoformans hsp70 antibody was detected in 16 of 24 (66.7%) patients with pulmonary cryptococcosis. Fourteen of 17 (82.3%) patients with high antigen titres (> or = 1:8) and two of seven (28.6%) patients with low titres (< or = 1:4) had detectable levels of anti-hsp70 antibody. Sera from patients positive for anti-hsp70 antibody showed high titres in the Eiken latex agglutination test for the detection of serum cryptococcal antigen. Our results indicate that the 70-kD hsp family from C. neoformans appears to be a major target molecule of the humoral response, not only in murine pulmonary cryptococcosis, but also in human patients with pulmonary cryptococcosis.

Extracellular Vesicles Produced by Cryptococcus neoformans Contain Protein Components Associated with Virulence

“…This group of molecules includes well-known virulence factors such as GXM and glucosylceramide, which were characterized as vesicle components in a previous study (45). In the present study, we demonstrate the presence of several other components associated with virulence in vesicular fractions, such as enzymes related to capsule synthesis (3), urease (11), laccase (46), acid phosphatase (8), heat shock proteins (25), and several antioxidant proteins such as superoxide dismutase (9,34), thioredoxin (29), thioredoxin reductase (30), thiol-specific antioxidant protein (31), and catalase A (22). Some of the vesicle proteins were recognized by sera from cryptococcosis patients, suggesting that these proteins are produced during human infection.…”

Cryptococcus neoformans Gene Expression during Experimental Cryptococcal Meningitis

“…In addition, the identification of HSP90 in our SAGE data is interesting, because the C. albicans Hsp90p is immunogenic and can confer protective immunity in a mouse model (58). HSP70 was also identified as highly abundant in vivo and is known to be a major immunogenic antigen during pulmonary cryptococcosis (42,43). Taken together, these studies with Hsp60p, Hsp70p, and Hsp90p in other fungi and our SAGE data suggest that all of these proteins can thus serve as good vaccine candidates for patients at risk for cryptococcal meningitis.…”

Schistosoma mansoni heat shock protein 70 elicits an early humoral immune response in S. mansoni infected baboons

“…Members of the hsp70 family of proteins have been extensively studied, since hsp70 proteins are one of the most abundant family of proteins expressed by all living organisms, both eukaryotic and prokaryotic (Kaufmann 1990, Mosely 2000. In spite of its high sequence conservation, the hsp70 has been shown to be an immunodominant target of the humoral and cellular response in infections caused by different bacterial, fungal, and parasite pathogens (Davenport et al 1992, Kakeya et al 1999, Oliveira-Ferreira et al 1999, Rico et al 1999.…”