The Walter and Eliza Hall Institute of Medical Research

Dr Diana Hansen

Details

Email: .(JavaScript must be enabled to view this email address)
Division: Infection and Immunity

Research Overview

Malaria is a major global disease responsible for over a million deaths each year. Clinical symptoms of malaria include respiratory distress, renal failure, pulmonary oedema and cerebral involvement. Blood-stage forms of Plasmodium parasites are responsible for such disease syndromes. After many years of exposure, individuals living in malaria-endemic areas develop a form of clinical immunity that protects from severe disease and symptomatic episodes by substantially reducing parasite burden. Antibodies against blood forms of Plasmodium parasites are thought to play an important role in mediating protective immunity.

The spleen is a crucial organ for blood-stage malaria clearance and the initiation of immune response to infection. However, acute malaria appears to cause dramatic changes to the structure of the spleen, which have been proposed to be a contributing factor for poor immunity. Lack of protection allows the parasite to replicate in the infected host. Mature forms of malaria parasites express surface proteins on the erythrocyte membrane, which allow them to bind to the vascular endothelium and avoid clearance in the spleen. This process, called sequestration is known to induce severe disease syndromes in target organs such as the brain and results in recruitment of host inflammatory leukocytes.

Studies have revealed that the spleen is the source of such inflammatory cells that migrate to target organs. Thus, immune responses appear to play a dual role in malaria by mediating protection against the parasite and contributing to pathogenesis, which highlights the balance that should take place to protect the host from infection without resulting in harmful inflammation.

Our group investigates the mechanisms by which inflammatory factors produced in response to infection modulate the balance between pathogenic organ-specific inflammation and spleen-mediated protective immunity to malaria. Understanding the mechanisms that control these inflammatory processes is highly relevant, as it could lead to the development of new therapeutic strategies to alleviate severe malaria syndromes and enable immune responses to be generated more effectively.

Research Interests

• Splenic architecture and induction of protective immunity to malaria
• Identification of antigens and host responses involved in immunity to human malaria
• Role of NK cells in malarial pathogenesis

Selected Publications

1. Nie CQ, Bernard NJ, Norman MU, Amante FH, Lundie RJ, Crabb BS, Heath WR, Engwerda CR, Hickey MJ, Schofield L, Hansen DS. IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection. PLoS Pathog. 2009, 5(4): e1000369. PubMed PMID: 19343215
2. Lundie RJ, de Koning-Ward TF, Davey GM, Nie CQ, Hansen DS, Lau LS, Mintern JD, Belz GT, Schofield L, Carbone FR, Villadangos JA, Crabb BS, Heath WR. Blood-stage Plasmodium infection induces CD8+ T lymphocytes to parasite-expressed antigens, largely regulated by CD8alpha+ dendritic cells. Proc Natl Acad Sci U S A. 2008, 105(38): 14509-14. PubMed PMID: 18799734
3. Hansen DS, D'Ombrain MC, Schofield L. The role of leukocytes bearing Natural Killer Complex receptors and Killer Immunoglobulin-like Receptors in the immunology of malaria. Curr Opin Immunol. 2007, 19(4): 416-23. PubMed PMID: 17702559
4. Hansen DS, Bernard NJ, Nie CQ, Schofield L. NK cells stimulate recruitment of CXCR3+ T cells to the brain during Plasmodium berghei-mediated cerebral malaria. J Immunol. 2007, 178(9): 5779-88. PubMed PMID: 17442962
5. Nie CQ, Bernard NJ, Schofield L, Hansen DS. CD4+ CD25+ regulatory T cells suppress CD4+ T-cell function and inhibit the development of Plasmodium berghei-specific TH1 responses involved in cerebral malaria pathogenesis. Infect Immun. 2007, 75(5): 2275-82. PubMed PMID: 17325053
6. Evans KJ, Hansen DS, van Rooijen N, Buckingham LA, Schofield L. Severe malarial anemia of low parasite burden in rodent models results from accelerated clearance of uninfected erythrocytes. Blood. 2006, 107(3): 1192-9. PubMed PMID: 16210332
7. Hansen DS, Evans KJ, D'Ombrain MC, Bernard NJ, Sexton AC, Buckingham L, Scalzo AA, Schofield L. The natural killer complex regulates severe malarial pathogenesis and influences acquired immune responses to Plasmodium berghei ANKA. Infect Immun. 2005, 73(4): 2288-97. PubMed PMID: 15784573
8. Hansen DS, Siomos MA, Buckingham L, Scalzo AA, Schofield L. Regulation of murine cerebral malaria pathogenesis by CD1d-restricted NKT cells and the natural killer complex. Immunity. 2003, 18(3): 391-402. PubMed PMID: 12648456.
9. Hansen DS, Siomos MA, De Koning-Ward T, Buckingham L, Crabb BS, Schofield L. CD1d-restricted NKT cells contribute to malarial splenomegaly and enhance parasite-specific antibody responses. Eur J Immunol. 2003, (9): 2588-98. PubMed PMID: 12938235
10. Schofield L, McConville MJ, Hansen D, Campbell AS, Fraser-Reid B, Grusby MJ, Tachado SD. CD1d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells. Science. 1999, 283(5399): 225-9. PubMed PMID: 9880256

Click here to view more PubMed publications

Current Laboratory Members

Faculty Member: Diana S Hansen, BSc(Hons) Buenos Aires PhD Buenos Aires

Postgraduate Student: Catherine Nie, BSc(Hons) Melb

Postgraduate Student: Victoria Ryg-Cornejo, BSc(Hons) Melb