The heat shock protein (Hsp) 70 of Cryptococcus neoformans is associated with the fungal cell surface and influences the interaction between yeast and host cells

Abstract

The pathogenic yeast Cryptococcus neoformans secretes numerous proteins, such as heat shock proteins, by unconventional mechanisms during its interaction with host cells. Hsp70 is a conserved chaperone that plays important roles in various cellular processes, including the interaction of fungi with host immune cells. Here, we report that sera from individuals with cryptococcosis infection recognize a recombinant C. neoformans Hsp70 (Cn_rHsp70). Moreover, immunofluorescence assays using antibodies against Cn_rHsp70 revealed the localization of this protein at the cell surface mainly in association with the capsular network. We found that the addition of Cn_rHsp70 positively modulated the interaction of C. neoformans with human alveolar epithelial cells and decreased fungal killing by mouse macrophages, without affecting phagocytosis rates. Immunofluorescence analysis showed that there was a competitive association among the receptor, GXM and Cn_rHsp70, indicating that the Hsp70-binding sites in host cells appear to be shared by glucuronoxylomannan (GXM), the major capsular antigen in C. neoformans. Our observations suggest additional mechanisms by which Hsp70 influences the interaction of C. neoformans with host cells.

Evaluating Common Humoral Responses against Fungal Infections with Yeast Protein Microarrays

“…Hsp70 is immunogenic in vivo in pulmonary cryptococcosis caused by the basidiomycete Cryptococcus neoformans (28,29). We also observed that other HSPs commonly reacted with the sera: HSP40/DnaJ family members (YNL064C, YNL077W) for sera after C.…”

Macrophage–Cryptococcus Interactions: An Update

“…In addition, soluble molecules can be found associated with the capsule, which often are released or shed, such as mannoprotein species (29–32). Recently, secreted C. neoformans heat shock protein-70 (hsp70) was described to have immune modulating properties (33). C. neoformans hsp70 bound to the surface of macrophages competing with GXM, therefore suggesting hsp70 recognition is through TLR4, TLR2, CD18 and/or CD14, all known receptors in the recognition of GXM (33, 34).…”

“…Recently, secreted C. neoformans heat shock protein-70 (hsp70) was described to have immune modulating properties (33). C. neoformans hsp70 bound to the surface of macrophages competing with GXM, therefore suggesting hsp70 recognition is through TLR4, TLR2, CD18 and/or CD14, all known receptors in the recognition of GXM (33, 34). Macrophage exposure to C. neoformans hsp70 resulted in decreased fungal killing as well as nitric oxide (NO) production and may represent a novel virulence factor.…”

Study of Humoral Responses against Lomentospora/Scedosporium spp. and Aspergillus fumigatus to Identify L. prolificans Antigens of Interest for Diagnosis and Treatment

“…The presence of Hsp70 on the cell surface [14] and its secretion makes it very accessible to the immune response and could explain its high immunogenicity. In addition, proteins of this family have been previously described as antigens [36][37][38] or virulence factors of important pathogenic fungi [48,49].…”