We focus on specific professional antigen presenting cells called dendritic cells (DCs), which are present at critical barriers in our body, such as skin and mucosa, to survey the surrounding environment for invading pathogens.
These DCs are not only crucial in inducing adaptive immunity but are also involved in innate immunity. DCs recognize pathogens through innate receptors and the subsequent signaling dictates the induction of adaptive immune responses by T cells. However, several pathogens, such as HIV-1, have subverted the function of DCs for their own dissemination in the host.
Therefore, elucidation of the molecular mechanisms involved in pathogen recognition and subsequent adaptive immunity will be instrumental in identifying general molecular processes as well as helping to counteract infections, such as preventing HIV-1 from hijacking DCs.
Our multidisciplinary research involves identification of pattern recognition receptors and intracellular signaling pathways that control infection and innate and adaptive immune responses to pathogens. In particular we investigate the role of C-type lectin receptors expressed by DC subsets in the interaction with pathogens.
We study the human immune system and therefore use primary DCs to perform our experiments. We generate monocyte-derived DCs from blood and isolate different DC subsets from skin that we obtain from plastic surgery via a long standing collaboration with the Boerhaave Medical Center Amsterdam (https://www.boerhaave.nl). Recently we have started to investigate mucosal DC subsets in vaginal tissues that we obtain from plastic surgery. The use of ex vivo tissue infection models as well as primary DC subsets allows us to create models that closely resemble the in vivo situation.
Recently we have started the Structural and functional characterization of MAVS-DDX3-vRNA complex. The mitochondrial antiviral signalling (MAVS) adaptor protein is a central signalling hub for host cells to mount an antiviral response following RNA virus infections, which is initiated by the cytosolic receptors that trigger the type-I interferon (IFNs) path through MAVS. Recently, it has been shown that the RNA helicase DDX3 is a novel atypical member of the viral cytosolic receptor family and it is required to activate the MAVS during the antiviral response against HIV-1. Currently, it is unknown how the complex partners MAVS-DDX3-vRNA (MDR) interact for assembly and what is the MDR mechanism of action at molecular level. Notably, silencing DDX3 or MAVS expression suppress activation of the native immune response, an event that in physiological condition is at the front line of host defence against virus such the HIV-1. However, understanding how viral RNA triggers the innate immune reaction requires the MDR structure elucidation. Moreover, these findings will allow to exploit MRD molecular features to create a new generation of adjuvants in anti-retroviral therapy. Our research addressed the structural and functional characterization of the MDR complex by biophysical and cellular biology techniques. This work will provide an understanding of how cellular protein sensors interact with retroviral RNA to trigger the native immune response and induce expression of antiviral proteins. (firstname.lastname@example.org, email@example.com)
We use a great variety of techniques from the fields of virology, biochemistry, molecular biology, cell biology and immunology.
Prof. Dr. Teunis Geijtenbeek (Principal investigator)
Dr. Sonja Gringhuis (Associate Professor)
Dr. Carla Ribeiro (Assistent Professor)
Ramin Sarrami-Forooshani (PhD student)
Joris Sprokholt (PhD student)
Maartje Nijmeijer (PhD student)
Nienke van Teijlingen (PhD student)
Nina Hertoghs (PhD student)
Melissa Stunnenberg (PhD student)
Leane Helgers (PhD student)
Tanja Kaptein (technician)
Ester Zijlstra-Willems (technician)
John van Hamme (technician)
Former lab members
Dr. Michiel van der Vlist
Dr. Alex Nabatov
Dr. Annemarie Lekkerkerker
Dr. Irene Ludwig
Dr. Jeroen van Dunnen
Dr. Lot de Witte
Dr. Marein de Jong
Dr. Stella Koppel
Dr. Angelic van der Aar
Dr. Brigitte Wevers
Dr. Daniele Amadio
Top 5 selected publications as senior author.
1. Ribeiro CM, Sarrami-Forooshani R, Setiawan LC, Zijlstra-Willems EM, van Hamme JL, Tigchelaar W, van der Wel NN, Kootstra NA, Gringhuis SI, Geijtenbeek TB. (2016). Receptor usage dictates HIV-1 restriction by human TRIM5alpha in dendritic cell subsets. Nature 540: 448-52 . (IF 38.1)
2. Gringhuis SI, Hertoghs N, Kaptein TM, Zijlstra-Willems EM, Sarrami-Fooroshani R, Sprokholt JK, van Teijlingen NH, Kootstra NA, Booiman T, van Dort KA, Ribeiro CM, Drewniak A, Geijtenbeek TB. (2017). HIV-1 blocks the signaling adaptor MAVS to evade antiviral host defense after sensing of abortive HIV-1 RNA by the host helicase DDX3. Nat Immunol 18: 225-35. (IF 19.4)
3. Geijtenbeek TB, Gringhuis SI. 2016. C-type lectin receptors in the control of T helper cell differentiation. Nat Rev Immunol 16: 433-48 . (IF 39.4)
4. Gringhuis,S.I., Kaptein,T.M., Wevers,B.A., Theelen,B., van,d., V, Boekhout,T., and Geijtenbeek,T.B. (2012). Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1beta via a noncanonical caspase-8 inflammasome. Nat. Immunol. 13, 246-254; . (IF 26.2).
5. Gringhuis,S.I., van de Vlist, M., van den Berg,L.M., den,Dunnen, J., Litjens,M., and Geijtenbeek,T.B. (2010). HIV-1 exploits innate signaling by TLR8 and DC-SIGN for productive infection of dendritic cells. Nat. Immunol. 11, 419-426. (IF 26.2)
For further information about our research and opportunities for work or collaborations, you can contact Prof. Teunis Geijtenbeek
+31 (0)20 566 6063