Spherules Derived from Coccidioides posadasii Promote Human Dendritic Cell Maturation and Activation

Abstract

Previous studies have shown that dendritic cells (DC) pulsed with T27K, an antigenic preparation derived from spherules (of Coccidioides posadasii), activate peripheral blood mononuclear cells (PBMC) from nonimmune subjects as well as from patients with disseminated coccidioidomycosis. In this study, we have assessed the interaction between human DC and C. posadasii spherules in order to better understand the initial response between Coccidioides and the human host. Whole autoclaved spherules induced lymphocyte transformation in PBMC obtained from immune but not from nonimmune donors. Immature DC (iDC) bound fluorescein isothiocyanate-labeled spherules in a time-and temperature-dependent manner. This binding was blocked by the addition of mannan, suggesting mannose receptor involvement in the DC-Coccidioides interaction. Binding was subsequently associated with ingestion and intracellular processing of spherules. Coculturing of spherules with iDC was associated with the development of mature DC that were morphologically, phenotypically, and functionally similar to those induced by tumor necrosis factor alpha and prostaglandin E 2 . Finally, spherules incubated with iDC induced activation of PBMC from nonimmune donors. These data indicate that human DC are capable of binding, internalizing, and presenting antigens from Coccidioides spherules and suggest that DC may play a critical early role in the formation of a cellular immune response in human coccidioidomycosis.

A Genetically Engineered Live Attenuated Vaccine ofCoccidioides posadasiiProtects BALB/c Mice against Coccidioidomycosis

“…The vaccine strain appeared to remain localized to sites of subcutaneous immunization. We suggest that immunization with the live spores followed by their differentiation into full-size spherules resulted in associated dendritic cell maturation and activation as reported by others (12). We also propose that as a result of the persistence of the live vaccine strain, progressive, acquired immunity against Coccidioides was effectively induced, and the immune response was much better tolerated by the mammalian host than vaccination with FKS.…”

Neither Dectin-2 nor the Mannose Receptor Is Required for Resistance to Coccidioides immitis in Mice

“…T27K stimulates human PBMC to secrete IL-2 and IFN-␥, and this response is blocked by soluble mannans. This group went on to show that immature heat-killed spherules are ingested by blood-derived DCs and their uptake is blocked by mannan (64). This was interpreted as evidence that the MR mediated those responses, although there are several mannose-binding receptors on PBMC.…”

Prophylactic and Therapeutic Vaccination Using Dendritic Cells Primed with Peptide 10 Derived from the 43-Kilodalton Glycoprotein of Paracoccidioides brasiliensis

“…T-cell activation and proliferation can lead to immunity or to tolerance, thus generating effector or regulatory T cells and different patterns of cytokines (36,37). The regulation of T-cell response by DCs in systemic and subcutaneous mycosis has been studied in Histoplasma capsulatum (15), Coccidioides posadasii (13), Sporothrix schenckii (44), and P. brasiliensis (1). The role of DCs in vaccination is a promising area for study.…”