Mechanisms of antigen cross-presentation
DCs are innate immune cells specialized in a type of antigen presentation termed cross-presentation that is paramount for immunity against intracellular pathogens, viruses and cancer. Immunotherapies are promising therapeutic strategies that often rely on eliciting cross-presentation. However, many are still poorly effective, in part due to the fact that mechanisms governing cross-presentation are not fully understood. Phagocytosis of antigens renders their cross-presentation more efficient, and several endoplasmic reticulum (ER)-localized proteins are required. However, the precise role that ER plays during cross-presentation has remained elusive. Our research in neutrophils identified a novel calcium signaling structure called membrane contact site (MCS), where the phagosomal and ER membranes are tightly juxtaposed. DCs have a 5-fold higher frequency of MCS, and MCS frequency correlates with cross-presentation efficiency, highlighting a novel relationship between the ER and phagosomes. Our present research is focused on exploring how MCS influence lipid transfer and membrane trafficking to and from phagosomes to promote cross-presentation, using state-of-the-art high-resolution and functional imaging techniques. We aim to clarify how the ER participates in regulating cross-presentation and to identify novel pathways that may be exploited to improve cross-presentation efficiency in formulations of DC-based immunotherapies.
Specific expertise
Prof. Nunes-Hasler has extensive experience in high-resolution microscopy, including 3D correlative light-electron microscopy (CLEM), and live functional imaging techniques such as ion (calcium, pH, ROS, chloride) imaging. Trained as a cell biologist, she has a comprehensive understanding of topics such as calcium signaling, ion fluxes and intracellular trafficking pathways including endocytic, phagocytic and exocytic pathways, as well as the emerging field of membrane contact sites. In addition, she has in-depth expertise in phagocyte biology including neutrophils, macrophages and dendritic cells.
Selected Publications
Nunes-Hasler P, Kaba M, Demaurex N. Molecular mechanisms of calcium signaling during phagocytosis. In: Molecular and cellular biology of phagocytosis. Cham: Springer; 2020 p. 103- 128.2
Nunes-Hasler P, Maschalidi S, Lippens C, Castelbou C, Bouvet S, Guido G, Bassoy EY, Page N, Merkler D, Hugues S, Martinvalet D, Manoury B, Demaurex N. STIM1 promotes migration, phagosomal maturation and antigen cross-presentation in dendritic cells. Nat Comm 2017 Nov 24;8(1):1852
Maschalidi S, Nunes-Hasler P, Nascimento C, Salent I, Lannoy V, Garfa-Traore M, Cagnard N, Vargas P, Lennon-Duménil AM, van-Endert P, Capiod T, Darasse-Jèze G, Demaurex N, Manoury B. UNC93B1 regulates cross presentation of antigens in dendritic cells via its association with the calcium sensor STIM1. Nat Comm 2017 Nov 21;8(1):1640
Guido D, Demaurex N*, Nunes P*. Junctate boosts phagocytosis by recruiting endoplasmic reticulum Ca2+ stores near phagosomes. J Cell Sci. 2015 Nov 15;128(22):4074-82
Nunes P, Cornut D, Bochet V, Ohora M, Waldburger JM, Demaurex N. STIM1 juxtaposes ER membranes to phagosomes generating localized Ca2+ signals that promote phagocytosis. Curr Biol 2012 Nov 6;22(21):1990-7
6 Nov 2020