Enhanced immunogenicity of pneumococcal surface adhesin A (PsaA) in mice via fusion to recombinant human B lymphocyte stimulator (BLyS).

Background: B lymphocyte stimulator (BLyS) is a member of the tumor necrosis factor superfamily of ligands that mediates its action through three known receptors. BLyS has been shown to enhance the production of antibodies against heterologous antigens when present at elevated concentrations, supporting an immunostimulatory role for BLyS in vivo.

Methods: We constructed a fusion protein consisting of human BLyS and Pneumococcal Surface Adhesin A (PsaA) and used this molecule to immunize mice.

Cell stress proteins: novel immunotherapeutics.

Heat shock proteins (HSPs) play important roles in the immune system as carriers of tumour antigens and inflammatory agents. The HSPs are abundantly expressed stress proteins intrinsic to all cellular life, permitting proteins to carry out essential enzymic, signalling and structural functions within the tightly crowded milieu of the cell. To carry out these tasks, HSPs are equipped with a domain that binds unstructured sequences in polypeptides and a N-terminal ATPase domain that controls the opening and closing of the peptide-binding domain.

Extracellular heat shock proteins in cell signaling and immunity.

Extracellular stress proteins including heat shock proteins (Hsps) and glucose-regulated proteins (Grps) are emerging as important mediators of intercellular signaling and transport. Release of such proteins from cells is triggered by physical trauma and behavioral stress as well as exposure to immunological "danger signals." Stress protein release occurs both through physiological secretion mechanisms and during cell death by necrosis.

Mechanisms for Hsp70 secretion: crossing membranes without a leader.

Heat shock protein 70 (Hsp70) is released from cells of many types and plays a significant signaling role, particularly in the inflammatory and immune responses. However, Hsp70 does not contain a consensus secretory signal and thus cannot traverse the plasma membrane by conventional mechanisms. However, Hsp70 can be released from cells by active mechanism that are independent of de novo Hsp70 synthesis or cell death.

Extracellular heat shock proteins in cell signaling.

Extracellular stress proteins including heat shock proteins (Hsp) and glucose regulated proteins (Grp) are emerging as important mediators of intercellular signaling and transport. Release of such proteins from cells is triggered by physical trauma and behavioral stress as well as exposure to immunological "danger signals". Stress protein release occurs both through physiological secretion mechanisms and during cell death by necrosis.

Heat shock protein 70 is secreted from tumor cells by a nonclassical pathway involving lysosomal endosomes.

Heat shock protein (HSP)70 can be released from tumor cells and stimulate a potent antitumor immune response. However, HSP70 does not contain a consensus secretory signal and thus cannot traverse the plasma membrane by conventional mechanisms. We have observed HSP70 release from intact human prostate carcinoma cell lines (PC-3 and LNCaP) by a mechanism independent of de novo HSP70 synthesis or cell death.

Heat induced release of Hsp70 from prostate carcinoma cells involves both active secretion and passive release from necrotic cells.

Purpose: Heat shock protein 70 (HSP70) is released from tumour cells and stimulates a potent anti-tumour immune response.

Methods: This study examined the role of hyperthermia, including heating conditions from the fever range, the hyperthermia range and the thermal ablation range, in HSP70 release from prostate carcinoma cells. It has observed HSP70 release from human prostate carcinoma cell lines (PC-3 and LNCaP) treated with hyperthermia.

Evaluation of antibody responses elicited by immunization of mice with a pneumococcal antigen genetically fused to murine HSP70 and murine interleukin-4.

The heat shock (stress) protein HSP70 has been shown to be a potent stimulator of cellular immune responses. In order to determine whether HSP70 has the ability to stimulate antibody responses, we constructed and expressed fusion proteins consisting of murine HSP70 or murine interleukin (IL)-4 covalently linked to a pneumococcal cell wall-associated protein antigen designated PpmA. Immunization of mice with the PpmA-HSP70 fusion protein (PpmA-70) failed to elicit an increased PpmA-specific serum antibody response.

Extracellular HSP70 binding to surface receptors present on antigen presenting cells and endothelial/epithelial cells.

Extracellular HSP70 has been found to participate in both innate and adaptive immune responses. However, little is known about the molecular mechanisms that mediate this process. Previous reports suggest that HSP70 interacts with antigen presenting cells (APC) through a plethora of surface receptors.

The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo.

In vitro studies have indicated the importance of Toll-like receptor (TLR) signaling in response to the fungal pathogens Candida albicans and Aspergillus fumigatus. However, the functional consequences of the complex interplay between fungal morphogenesis and TLR signaling in vivo remain largely undefined. In this study we evaluate the impact of the IL-1R/TLR/myeloid differentiation primary response gene 88 (MyD88)-dependent signaling pathway on the innate and adaptive Th immunities to C.

The antifungal drug amphotericin B promotes inflammatory cytokine release by a Toll-like receptor- and CD14-dependent mechanism.

Amphotericin B is the most effective drug for treating many life-threatening fungal infections. Amphotericin B administration is limited by infusion-related toxicity, including fever and chills, an effect postulated to result from proinflammatory cytokine production by innate immune cells. Because amphotericin B is a microbial product, we hypothesized that it stimulates immune cells via Toll-like receptors (TLRs) and CD14.

Toll-like receptor (TLR) signaling in response to Aspergillus fumigatus.

Aspergillus fumigatus causes life-threatening infections in patients with qualitative and quantitative defects in phagocytic function. Here, we examined the contribution of Toll-like receptor (TLR)-2, TLR4, the adapter protein MyD88, and CD14 to signaling in response to the three forms of A. fumigatus encountered during human disease: resting conidia (RC), swollen conidia (SC), and hyphae (H).