Research Groups

Cytokines and Disease

Research Interests and Description
Group Leader: Frank Brombacher, PhD

Group Members

Research Interests

Immunological mechanisms of host protection in infectious and non-infectious diseases.
Biological role of aaMph's

Description of Research

The Group investigates immunological mechanisms in experimental murine models for human diseases. Major general topics include cytokine network and regulation, lymphocytes differentiation and function, dendritic cell and macrophage activation, as well as the role of non-immunological effector cells in health/disease like smooth muscle cells, goblet cells, activated by IL-4 and IL13. Current disease models under investigations include:

Bacterial Infectious Diseases
• Tuberculosis caused by Mycobacterium tuberculosis (aerosol)
• Listeriosis caused by Listeria monocytogenes

Parasitic Infectious Diseases
• African trypanosomiasis caused by Trypanosoma brucei/evansi/congolense
• Cutaneous leishmaniasis caused by Leishmania major
• Schistosomiasis (Bilharzia) caused by Schistosoma mansoni
• Hookworm caused by Nippostrongylus brasiliensis

Non-infectious Diseases
Allergic inflammation, induced by Ovalbumin and Anisakis
Colitis, chemically induced by Oxazalone
Fibrosis, chemically induced by Bleomycin

Our research strategy is based on gain of knowledge by a loss of function approaches in knockout and knockdown animal models. This includes the generation and characterisation of novel conditional gene deficient mouse strains (Table 1). Together with transcriptomic approaches the significance of genes, factors and cells for host protection and failure thereof are uncovered and possible factors for host-directed drug targeting identified. This support our long-term goal for the development of safe and cost- effective drug and vaccination strategies.

Recent Publications

Dewals, B., Hoving, J.C., Leeto, M., Marillier, R.G., Govender, U., Cutler, A.J., Horsnell, W.G.C., Brombacher, F. 2009. IL-4Ra responsiveness of non-CD4 T cells contributes to resistance in Schistosoma mansoni infection investigated in pan-T cell-specific IL-4Rα-deficient mice. J. Am. Pathol. 175, 706-716

Brombacher, F., Arendse, B., Peterson, R., Hölscher, A., Hölscher, C. 2009. Analyzing classical and alternative macrophage activation in macrophage/neutrophil-specific IL-4 receptor-alpha-deficient mice. Methods Mol Biol. 531, 225-252

Magez, S., Schwegmann, A.,  Atkinson, R., Claes, F., Drennan, M., De Baetselier, P., Brombacher. F. 2008. The role of B-cells and IgM antibodies in paratemia, anemia, and VSG switching in Trypanosoma brucei-infected mice. PLoSpathogen 4, e000122

Schwegmann, A., Brombacher, F. 2008. Host-directed drug targeting of factors hijacked by pathogens. Science Signaling 1, re8

Schwegmann, A., Guler, R., Cutler, A.J., Arendse, B., Horsnell, W.G., Flemming, A., Kottmann, A.H., Ryan, G., Hide, W., Leitges, M., Seoighe, C., Brombacher, F. 2007. Protein kinase C {delta} is essential for optimal macrophage-mediated phagosomal containment of Listeria monocytogenes. PNAS 104, 16251-16256

Horsnell, W.G.C., Cutler, A.J., Hoving, C., Mearns, H., Myburg, E., Arendse, B., Finkelman, F.D., Owens, G.K., Erle, D., Brombacher, F. 2007. Delayed goblet cell hyperplasia and worm expulsion in smooth muscle cell specific IL-4Ra deficient mice. PLoSpathogen, 162, 7302-7308

ICGEB Cape Town

Wernher and Beit Building (South)
UCT Campus
Anzio Road
Observatory 7925
Cape Town
SOUTH AFRICA
Tel: +27-21-4066335
Fax: +27-21-4066060
icgeb@icgeb.org
Developing Knowledge