Mannoproteins of Cryptococcus neoformans induce proliferative response in human peripheral blood mononuclear cells (PBMC) and enhance HIV-1 replication

Abstract

To investigate the possible role of Cryptococcus neoformans var. neoformans in HIV disease progression, and to identify the responsible cryptococcal components, an in vitro cell culture model was set up to study the C. neoformans‐induced enhancement of HIV replication in HIV‐1‐infected PBMC. Similar to whole C. neoformans, cell‐wall membrane fraction and mannoproteins induced proliferation of PBMC and enhancement of lymphotropic HIV replication in HIV‐infected PBMC, while galactoxylomannan did not. MoAbs capable of interfering with MHC class II‐mediated antigen presentation prevented the induction of cell proliferation by whole C. neoformans or cryptococcal mannoproteins. MoAb binding to adhesion molecules intercellular adhesion molecule‐1 (ICAM‐1) and lymphocyte function‐associated antigen‐1 (LFA‐1) also inhibited C. neoformans‐induced cell proliferation. In addition, anti‐MHC class II MoAb inhibited the enhancement of HIV replication by C. neoformans. The results suggest that: (i) C. neoformans may accelerate HIV disease progression by stimulation of HIV replication through MHC class II‐mediated antigen presentation; and (ii) cryptococcal mannoprotein may be one of the responsible components. The ability to enhance HIV replication in PBMC in vitro is not unique for C. neoformans. However, this is the first report to study in detail a yeast‐induced enhancement of HIV replication in PBMC.

Mannoprotein fromCryptococcus neoformansPromotes T-Helper Type 1 Anticandidal Responses in Mice

“…MPs of C. neoformans have been identified elsewhere as the major antigens inducing CMI responses to C. neoformans (17), including DTH elicitation, T-cell activation, and cytokine production by peripheral blood mononuclear cells (4,19,22). More recently the molecular characterization of a C. neoformans MP that stimulates a T-cell response has been provided (13,14).…”

“…In particular, Candida and Cryptococcus MPs were shown elsewhere to induce lymphoproliferation (19,23) and cytokine production (21,22,27). Previous data showed that interleukin-12 (IL-12) plays a pivotal role in induction of the Thelper type 1 (Th1) response against C. neoformans infection, this response being essential for protection (6).…”

Role of Mannoprotein in Induction and Regulation of Immunity toCryptococcus neoformans

“…Purification of MP (fraction II) was performed by affinity chromatography (concanavalin A) and anion-exchange chromatography (DEAE) (2). Anion-exchange chromatography of the MPs yielded two fractions, MP1 (35.6 kDa) and MP2 (8.2 kDa) (24). In this study MP2, which consists of 13.3% protein and 43% carbohydrate (2), was used.…”

“…MP also promotes T-cell activation (24,26) and induction of tumor necrosis factor alpha (TNF-␣) secretion by monocytes (1). Recently we demonstrated that MP induces strong and early production of interleukin (IL)-12 by human monocytes, resulting in early induction of gamma interferon (IFN-␥) secretion by T cells (25).…”

Optimal T Cell Responses to Cryptococcus neoformans Mannoprotein Are Dependent on Recognition of Conjugated Carbohydrates by Mannose Receptors

“…52817; American Type Culture Collection, Manassas, VA) as previously described (34), with minor modifications. Briefly, fungi were grown for 5 days at 30°C in an orbital shaker in medium consisting of 6.7 g/L yeast nitrogen base, 27 mM dextrose, 64 M L-histidine, 134 M L-methionine, and 97 M L-tryptophan.…”