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Wykes M.N.,The Queensland Institute of Medical Research
Trends in Parasitology

Dendritic cells (DCs), the sentinels of immunity, reside in almost every organ of the body. These cells are responsible for initiating immune responses against infectious agents. DCs are divided into different subsets based on their biological functions, with plasmacytoid DCs (pDCs) and conventional DCs (cDCs) being two major populations. The ability of DCs to protect against malaria infection was recently questioned when pDCs were reported to be a reservoir for rodent . Plasmodium spp. in the spleen. This opinion article explores how the occupation of pDCs by the parasite may corrupt immunity against malaria. © 2012 Elsevier Ltd. Source

Koyama M.,The Queensland Institute of Medical Research

Donor T cells play pivotal roles in graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects following bone marrow transplantation (BMT). DNAX accessory molecule 1 (DNAM-1) is a costimulatory and adhesion molecule, expressed mainly by natural killer cells and CD8(+) T cells at steady state to promote adhesion to ligand-expressing targets and enhance cytolysis. We have analyzed the role of this pathway in GVHD and GVL. The absence of DNAM-1 on the donor graft attenuated GVHD in major histocompatibility complex (MHC)-mismatched and MHC-matched BMT following conditioning with lethal and sublethal irradiation. In contrast, DNAM-1 was not critical for GVL effects against ligand (CD155) expressing and nonexpressing leukemia. The effects on GVHD following myeloablative conditioning were independent of CD8(+) T cells and dependent on CD4(+) T cells, and specifically donor FoxP3(+) regulatory T cells (Treg). The absence of DNAM-1 promoted the expansion and suppressive function of Treg after BMT. These findings provide support for therapeutic DNAM-1 inhibition to promote tolerance in relevant inflammatory-based diseases characterized by T-cell activation. Source

Anthony B.J.,The Queensland Institute of Medical Research | Ramm G.A.,The Queensland Institute of Medical Research | Ramm G.A.,University of Queensland | McManus D.P.,The Queensland Institute of Medical Research
Trends in Parasitology

Pathology in schistosomiasis occurs as a result of eggs deposited in the liver by the schistosome parasite. A granulomatous reaction occurs, resulting in portal hypertension and hepatic fibrosis. Resident non-parenchymal cells within the liver take part in this process, including hepatic stellate cells, which are responsible for collagen production, and Kupffer cells, the liver macrophages involved in both host protection and in pathology. Other cells such as liver sinusoidal endothelial cells or portal fibroblasts may also be involved in this process. This review discusses the possible role of these resident liver cells in the pathology associated with schistosomiasis and provides information which may assist our understanding of the mechanisms associated with chronic liver disease in general. © 2012 Elsevier Ltd. Source

Engwerda C.R.,The Queensland Institute of Medical Research | Engwerda C.R.,University of Queensland | Minigo G.,Charles Darwin University | Amante F.H.,The Queensland Institute of Medical Research | And 2 more authors.
Trends in Parasitology

A system for experimentally induced blood stage malaria infection (IBSM) with Plasmodium falciparum by direct intravenous inoculation of infected erythrocytes was developed at the Queensland Institute of Medical Research (QIMR) more than 15 years ago. Since that time, this system has been used in several studies to investigate the protective effect of vaccines, the clearance kinetics of parasites following drug treatment, and to improve understanding of the early events in blood stage infection. In this article, we will review the development of IBSM and the applications for which it is being employed. We will discuss the advantages and disadvantages of IBSM, and finish by describing some exciting new areas of research that have been made possible by this system. © 2012. Source

Wykes M.N.,The Queensland Institute of Medical Research | Horne-Debets J.,The Queensland Institute of Medical Research
International Journal for Parasitology

Malaria, caused by . Plasmodium spp., is responsible for over 200. million infections worldwide and 650,000 deaths annually. Until recently, it was thought that blood-stage parasites survived and replicated in hepatocytes and red blood cells exclusively. We recently showed that blood-stage parasites could infect, survive and replicate within plasmacytoid dendritic cells of the spleen and that these cells could release infective parasites. Here we discuss the implications of this novel niche in the spleen. © 2012 . Source

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