6 | Microglial-endothelial interaction in the regulation of leucocyte recruitment

How microglia influence endothelial gate-keeper functions during the recruitment of leucocytes is largely unclear, as tools to selectively modulate microglial function have only recently become available. Our work has shown that microglial cells form contacts with both nearby neurons and capillaries, and that the absence of microglia results in augmented brain injury after stroke (Szalay et al., 2016). Our recent research has revealed the role of microglia and site-specific IL-1 actions in the regulation of leukocyte recruitment and vascular responses (Fekete et al., 2018; Wong et al., 2018) and the role of microglia in shaping cerebral blood flow (unpublished). Using cutting-edge imaging techniques established at IEMHAS, such as super-resolution microscopy, laser speckle contrast imaging, electron tomography, in vivo 2-photon imaging, and selective modulation of microglial inflammatory responses, we will investigate how microglial-endothelial interactions influence leucocyte recruitment across endothelial barriers.

Publications

  • Fekete R, Cserép C, Lénárt N, Tóth K, Orsolits B, Martinecz B, Méhes E, Szabó B, Németh V, Gönci B, Sperlágh B, Boldogkői Z, Kittel Á, Baranyi M, Ferenczi S, Kovács K, Szalay G, Rózsa B, Webb C, Kovacs GG, Hortobágyi T, West BL, Környei Z, Dénes Á*. Microglia control the spread of neurotropic virus infection via P2Y12 signalling and recruit monocytes through P2Y12-independent mechanisms. Acta Neuropathol. 2018;36:461-482.
  • Wong R, Lénárt N, Hill L, Toms L, Coutts G, Martinecz B, Császár E, Nyiri G, Papaemmanouil A, Waisman A, Müller W, Schwaninger M, Rothwell N, Francis S, Pinteaux E, Denes A*, Allan SM*. Interleukin-1 mediates ischaemic brain injury via distinct actions on endothelial cells and cholinergic neurons. Brain Behav Immun. 2019;76:126-138.
  • Szalay G, Martinecz B, Lénárt N, Környei Z, Orsolits B, Judák L, Császár E, Fekete R, West B.L., Katona G, Rózsa B, Dénes Á*. Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke. Nat Commun 2016;7:11499.
  • Szigeti K, Horváth I, Veres DS, Martinecz B, Lénárt N, Kovács N, Bakcsa E, Márta A, Semjéni M, Máthé D, Dénes Á*. A novel SPECT-based approach reveals early mechanisms of central and peripheral inflammation after cerebral ischemia. J Cereb Blood Flow Metab 2015;35:1921-9.
  • Denes A*, Coutts G, Lénárt N, Cruickshank SM, Pelegrin P, Skinner J, Rothwell N, Allan SM, Brough D*. AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3. Proc Natl Acad Sci U S A 2015;112:4050-4055.


Potential secondments

UHEL (Jari Koistinaho), month 12-13; INSERM (Denis Vivien), month 16-17; UNIBERN (Britta Engelhardt), month 33; WWU (Lydia Sorokin), month 35-36

Host Organisation:
Institute of Experimental Medicine, Hungarian Academy of Science, Budapest,Hungary
Supervisor:
Ádám Dénes