INFECTIOUS DISEASES / Parasitic Diseases
Immunological mechanisms of host protection in infectious and non-infectious diseases.
Description of Research
The Group investigates immunological mechanisms in experimental murine models for human diseases. Major general topics include cytokine network and regulation, lymphocyte 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.
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. 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 supports our long-term goal for the development of safe and cost-effective drug and vaccination strategies.
Brombacher, T.M., De Gouveia, K.S., Cruywagen, L., Makena, N., Booley, F., Tamgue, O., Brombacher, F. 2018. Nippostrongylus brasiliensis infection leads to impaired reference memory and myeloid cell interference. Sci Rep 8, 2958 PubMed link
Hurdayal, R., Ndlovu, H.H., Revaz-Breton, M., Parihar, S.P., Nono, J.K., Govender, M., Brombacher, F. 2017. IL-4-producing B cells regulate T helper cell dichotomy in type 1- and type 2-controlled diseases. Proc Natl Acad Sci USA 114, E8430-E8439 PubMed link
Parihar, S.P., Ozturk, M., Marakalala, M.J., Loots, D.T., Hurdayal, R., Beukes, D., Van Reenen, M., Zak, D.E., Mbandi, S.K., Darboe, F., Penn-Nicholson, A., Hanekom, W.A., Leitges, M., Scriba, T.J., Guler, R., Brombacher, F. 2017. Protein kinase C-delta (PKCδ), a marker of inflammation and tuberculosis disease progression in humans, is important for optimal macrophage killing effector functions and survival in mice. Mucosal Immunol 11, 579 PubMed link
Nono, J.K., Ndlovu, H., Abdel Aziz, N., Mpotje, T., Hlaka, L., Brombacher, F. 2017. Host regulation of liver fibroproliferative pathology during experimental schistosomiasis via interleukin-4 receptor alpha. PLoS Negl Trop Dis 11, e0005861 PubMed link
Nono, J.K., Ndlovu, H., Abdel Aziz, N., Mpotje, T., Hlaka, L., Brombacher, F. 2017. Interleukin-4 receptor alpha is still required after Th2 polarization for the maintenance and the recall of protective immunity to Nematode infection. PLoS Negl Trop Dis 11, e0005675 PubMed link
Hoving, J.C., Cutler, A.J., Leeto, M., Horsnell, W.G., Dewals, B.G., Nieuwenhuizen, N.E., Brombacher, F. 2017. Interleukin 13-mediated colitis in the absence of IL-4Ra signalling. Gut. 66: 2037-2039