Myeloid Cell Immunology
Over the years, the cellular immunology group has developed several experimental model systems that allow a detailed study of the mechanisms governing immune modulation in both normal and pathological conditions. In-house disease models include parasitic infections, such as African trypanosomosis and helminth infection, and cancer. More recently, the field of innate immunity, in particular the immunobiology of myeloid cells (MCs), became a central research topic.
MCs (including monocytes, macrophages and dendritic cells) are crucial innate effectors, immunomodulators and/or antigen presenting cells that can acquire different functional activation states depending on which immune and microbial stimuli they are exposed to. As such, MCs represent interesting targets for intervention during inflammatory/anti-inflammatory processes. Moreover, tools to monitor the activation/differentiation state of MCs would allow to use these cells as in vivo sensors in prognosis and thera(g)nosis of pathologies, as well as in therapy follow-up and screening of immunomodulators.
Our strategic vision is to use the heterogeneity of MCs (mainly monocytes, macrophages and dendritic cells) as an in vivo sensor to track inflammatory responses and as a target for therapeutic intervention. In the past, we have mainly been focused on heterogeneity of tissue-associated monocytic cells at the level of their activation states. Recent evidence (including our own) suggests that tissue-associated MCs contain different subpopulations, including resident and recruited monocyte-derived cells that can both differentiate into antigen presenting cells upon activation/inflammation. Thus, we are gradually shifting the focus to heterogeneity at the level of different subpopulations of MCs present in selected inflamed tissues, in particular in the liver (Kupffer cells) and tumors (hypoxic and normoxic tumor-associated macrophages). Also the so-called myeloid-derived suppressor cells (MDSCs) represent an important research focus.
Based on markers that allow discriminating selected MC subpopulations, we invest in the development of tools to visualize and modulate the in vivo differentiation, recruitment and function of selected MC subpopulations in inflamed tissues. These include the generation of transgenic mice allowing tracking and ablating of selected MC populations to evaluate their role in distinct models of liver injury and tumor growth. We also exploit the strategic advantage of Nanobodies as tools for in vivo imaging and therapeutic targeting of MCs.
The main inflammatory diseases under study are (i) infectious diseases, with an important focus on African trypanosome infections, (ii) inflammation, with an important focus on liver inflammation, and (iii) cancer. Through collaborative networks, we are also studying a range of other inflammatory diseases such as atherosclerosis, rheumatoid arthritis and pulmonary inflammation, as well as associated pathological features (such as anemia).
- Molecular profiling reveals a tumor-promoting phenotype of monocytes and macrophages in human cancer progression Chittezhath M, Dhillon M, Lim J, Laoui D, Shalova I, Teo Y, Chen J, Kamaraj R, Raman L, Lum J, Thamboo T, Chiong E, Zolezzi F, Yang h, Van Ginderachter J, Poidinger M, Wong A, Biswas S. IMMUNITY, 41, 815-29, 2014
- Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage population Laoui D, Van Overmeire E, Di Conza G, Aldeni C, Keirsse J, Morias Y, Movahedi K, Houbracken I, Schouppe E, Elkrim Y, Karroum O, Jordan B, Carmeliet P, Gysemans C, De Baetselier P, Mazzone M, Van Ginderachter J. CANCER RESEARCH, 74, 24-30, 2014
- MIF Contributes to Trypanosoma brucei Associated Immunopathogenicity Development Stijlemans B Leng L Brys L Sparkes A Vansintjan L Caljon G Raes G Van Den Abbeele J Van Ginderachter J Beschin A Bucala R* De Baetselier P*. PLoS Pathogens, 10, e1004414, 2014* These authors contributed equally
- Adenylate cyclases of Trypanosoma brucei inhibit the innate immune response of the host Salmon D, Vanwalleghem G, Morias Y, Denoeud J, Krumbholz C, Lhommé F, Bachmaier S, Kador M, Gossmann J, Dias F, De Muylder G, Uzureau P, Magez S, Moser M, De Baetselier P, Van Den Abbeele J, Beschin A, Boshart M, Pays E. SCIENCE, 337, 463-6, 2012
- Nanobody-based targeting of the macrophage mannose receptor for effective in vivo imaging of tumor-associated macrophages Movahedi K, Schoonooghe S, Laoui D, Houbracken I, Waelput W, Breckpot K, Bouwens L, Lahoutte T, De Baetselier P, Raes G, Devoogdt N, Van Ginderachter J. CANCER RESEARCH, 72, 4165-77, 2012