Immunology & Infection

Staff
Funding
Collaborators
Student Projects
Key Recent Publications
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Lab Head: Dr Christian Engwerda
Christian.Engwerda@qimr.edu.au

The Immunology and Infection Laboratory was established at QIMR in 2003 by Dr Christian Engwerda to study immunology and pathology during experimental cerebral malaria and visceral leishmaniasis.

Cerebral malaria
Malaria remains one of the world’s greatest health problems, and cerebral malaria (CM) is a major cause of death in African children infected with Plasmodium falciparum. This serious neurological condition is characterised by the sequestration of parasitised red blood cells (pRBC) in cerebral blood vessels. Because high levels of circulating tumour necrosis factor alpha (TNFa) are found in the serum of CM patients, this cytokine is thought to play an essential role in the development of pathology associated with CM. However, we have recently identified lymphotoxin alpha (LTa), a related member of the TNF family, and not TNFa, as a key mediator of CM. We are now characterising the precise role of LTa during CM to try and devise strategies to modulate the activities of this molecule during human infections.

Plasmodium berghei ANKA infection in the brain
From left: an electron micrograph showing a parasitised red blood cell (arrowed) in a cerebral vessel;
perivascular haemorrhages (arrowed) in the cerebellum of the brain of a mouse with cerebral malaria;
parasites (green) in red blood cells that have accumulated in the cerebral vessels of mice with cerebral malaria.

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Visceral leishmaniasis
VL is a potentially fatal human disease caused by the intracellular protozoan parasites Leishmania donovani and L. infantum (chagasi). These parasites infect mature tissue macrophages throughout the viscera, though the spleen and liver are the major sites of disease. VL can be characterised by organ-specific immunity, whereby the liver is a site of an acute, resolving infection and a chronic infection becomes established in the spleen. We are primarily interested in defining the basis for organ-specific immunity during VL. We recently discovered that macrophage populations in spleen and liver respond very differently to infection with L. donovani. We are now identifying the specific immune mechanisms that are activated in the spleen and liver during VL, and determining how these mechanisms impact on the survival and function of infected macrophages. This research will provide a more rational basis from which to design effective vaccines and therapies to control VL and other infectious diseases.

Leishmania donovani infection in the spleen and liver
A. an electron micrograph showing amastigotes (arrowed) in the phagolysosome of a macrophage in the spleen. Note the interaction with surrounding lymphocytes;
B. IL-12 production (brown) by dendritic cells in the T cell areas of the spleen 5 hours after infection. Marginal zone macrophages (a target for infection) are stained black with india ink;
C. IL-12 production (brown) in the developing granuloma around infected Kupffer cells in the liver 28 days after infection.

Staff

Funding

The Wellcome Trust
The National Health and Medical Research Council

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Collaborators

• Dr Paul Kaye, London School of Hygiene and Tropical Medicine, UK
• Dr Dale Godfrey, University of Melbourne, Melbourne
• Dr Mark Smyth, Peter MacCallum Hospital, Melbourne
• Dr Carl Ware, La Jolla Institute for Allergy and Immunology, USA
• Dr Koji Tamada, Johns Hopkins University, USA

Student Projects

The Imunnology and Infection Laboratory has a number of projects available for students. Please contact Chris Engwerda for details.

Key Publications

Amante, F. H., A. C. Stanley, L. M. Randall, Y. Zhou, A. P. Waters, C. J. Janse, M. F. Good, G. R. Hill and C. R. Engwerda. 2007. A role for natural regulatory T cells in the pathogenesis of experimental cerebral malaria. Am J Path 171: 548 [pubmed abstract]

DeWalick, S., F. H. Amante, L. M. Randall, Y, Zhou, K. P. A. MacDonald, G. R. Hill and C. R. Engwerda. 2007. Cutting Edge: Conventional dendritic cells, but not plasmacytoid dendritic cells, mediate experimental cerebral malaria caused by Plasmodium berghei ANKA. J Immunol 178: 6033 [pubmed abstract]

Good M.F., Xu H., Wykes M., Engwerda C.R. 2005. Development and regulation of cell-mediated immune responses to the blood stages of malaria: Implications for Vaccine Research. Annu Rev Immunol 23:69-99. [pubmed abstract]

Engwerda CR, Beattie L, Amante FH. 2005. The importance of the spleen in malaria. Trends Parasitol 21(2):75-80. Review. [pubmed abstract]

Engwerda CR., Ato M., Stager S., Alexander CE., Stanley A.C., Kaye P.M. 2004. Distinct roles for lymphotoxin alpha and TNF in murine visceral leishmanaisis. Am J Pathol 165: 2123 [pubmed abstract]

Kaye P.M., Svensson M., Ato M., Maroof A., Polley R., Stager S., Zubairi S., Engwerda C.R. 2004. The immunopathology of experimental visceral leishmaniasis. Immunol Rev 201:239. [pubmed abstract]

Engwerda C.R., Ato M., Kaye P.M.. 2004. Macrophages, pathology and parasite persistence in experimental visceral leishmaniasis. Trends in Parasitol 20:524. [pubmed abstract]

Ato, M., S. Stager, C. R. Engwerda and P. M. Kaye. 2002. Defective CCR7 expression on dendritic cells contributes to the development of chronic visceral leishmanisis. Nature Immunology 3:1185 [pubmed abstract]

Engwerda, C. R., T. L. Mynott, S. Sawhney, J. B. De Souza, Q. Bickle and P. M. Kaye. 2002. Lymphotoxin-a, not Tumor Necrosis Factor-a, is the principle mediator in murine cerebral malaria. J Exp Med 195:1371.[pubmed abstract]

Engwerda, C. R., M. Ato, S. E. J. Cotterell, A. Tschannerl, P. Gorak-Stolinska and P. M. Kaye. 2002. Remodelling of the splenic marginal zone during Leishmania donovani infection is mediated by TNFa. Am J Path 161:429.[pubmed abstract]

Alexander, C. E., P. M. Kaye, and C. R. Engwerda. 2001. A role for CD95 in the control of murine visceral leishmaniasis caused by Leishmania donovani. Eur J Immunol 31:1199.[pubmed abstract]

Engwerda, C. R. and P. M. Kaye. 2000. Organ-specific immune responses associated with infectious disease. Immunol Today 21:73.[pubmed abstract]

Mynott, T. L., A. Ladhams, P. Scarmato, and C. R. Engwerda. 1999. Bromelain, from pineapple stems, proteolytically blocks activation of extracellular regulated kinase-2 in T cells. J Immunol 163:2568.[pubmed abstract]

Engwerda, C. R., M. L. Murphy, S. E. Cotterell, S. C. Smelt, and P. M. Kaye. 1998. Neutralization of IL-12 demonstrates the existence of discrete organ- specific phases in the control of Leishmania donovani. Eur J Immunol 28:669.[pubmed abstract]

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