Microglia and border-associated macrophages play opposite roles in cerebrovascular and leukocyte responses under systemic inflammation in male mice.
11 affiliations
- 1"Momentum" Laboratory of Neuroimmunology, HUN-REN Institute of Experimental Medicine, Budapest, Hungary.
- 2János Szentágothai Doctoral School of Neurosciences, Schools of PhD Studies, Semmelweis University, Budapest, Hungary.
- 3Normandie University, Caen Normandie University, UNICAEN, INSERM U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), Caen, France.
- 4Department of Neuroscience, Yale School of Medicine, Yale University, 333 Cedar Street, New Haven, CT, USA.
- 5Hungarian Centre of Excellence for Molecular Medicine - University of Szeged, Cerebral Blood Flow and Metabolism Research Group, Szeged, Hungary.
- 6Department of Cell Biology and Molecular Medicine, Albert Szent-Györgyi Medical School and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
- 7Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Munster, Germany.
- 8Cells-in-Motion Interfaculty Centre (CIMIC), University of Münster, Münster, Germany.
- 9Centre for Inflammation Research Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
- 10Department of Clinical Research, Caen University Hospital, Caen, France.
- 11"Momentum" Laboratory of Neuroimmunology, HUN-REN Institute of Experimental Medicine, Budapest, Hungary. [email protected].
Abstract
Microglia closely associate with the vasculature, but their roles in leukocyte trafficking and cerebral blood flow (CBF) during systemic inflammation are unclear. We show that sustained systemic inflammation leads to altered microglia-vascular interactions, leukocyte recruitment to cerebral blood vessels and reduced hypercapnia-induced vasodilation. We find that microglia and border-associated macrophages (BAMs) play distinct roles in these processes: while BAM depletion with clodronate increases leukocyte recruitment, microglia/BAM depletion with PLX5622 and the absence of microglia, but not BAMs in CSF1RΔFIRE/ΔFIRE mice, result in markedly reduced leukocyte recruitment. Supporting this, conditional microglial IL-1 deletion inhibits leukocyte recruitment. Unlike BAM depletion, the absence of microglia impairs hypercapnia-induced vasodilation, while in vivo two-photon imaging reveals microglial IL-1α-dependent interactions between leukocytes and penetrating arteries. Accordingly, reduced hypercapnia-induced vasodilation involves endothelial IL-1R1 and microglial IL-1α. Thus, distinct brain macrophage populations exert opposite effects on leukocyte recruitment and CBF through IL-1 dependent mechanisms in given vascular beds in male mice.
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BibTeX
@article{bras2026microglia,
title = {{Microglia and border-associated macrophages play opposite roles in cerebrovascular and leukocyte responses under systemic inflammation in male mice.}},
author = {Ana Rita Brás and Nikolett Lénárt and Damien Levard and Martina Glavan and Ákos Menyhárt and Csaba Cserép and Balázs Pósfai and Eszter Császár and Sai K Reddy Samawar and Clare Pridans and Denis Vivien and Eszter Farkas and Lydia Sorokin and Marina Rubio and Ádám Dénes},
journal = {Nature communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77787-4},
url = {https://europepmc.org/article/MED/42897171},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Microglia and border-associated macrophages play opposite roles in cerebrovascular and leukocyte responses under systemic inflammation in male mice.
AU - Ana Rita Brás
AU - Nikolett Lénárt
AU - Damien Levard
AU - Martina Glavan
AU - Ákos Menyhárt
AU - Csaba Cserép
AU - Balázs Pósfai
AU - Eszter Császár
AU - Sai K Reddy Samawar
AU - Clare Pridans
AU - Denis Vivien
AU - Eszter Farkas
AU - Lydia Sorokin
AU - Marina Rubio
AU - Ádám Dénes
PY - 2026
DA - 2026/09/18
JO - Nature communications
DO - 10.1038/s41467-026-77787-4
UR - https://europepmc.org/article/MED/42897171
AB - Microglia closely associate with the vasculature, but their roles in leukocyte trafficking and cerebral blood flow (CBF) during systemic inflammation are unclear. We show that sustained systemic inflammation leads to altered microglia-vascular interactions, leukocyte recruitment to cerebral blood vessels and reduced hypercapnia-induced vasodilation. We find that microglia and border-associated macrophages (BAMs) play distinct roles in these processes: while BAM depletion with clodronate increases leukocyte recruitment, microglia/BAM depletion with PLX5622 and the absence of microglia, but not BAMs in CSF1RΔFIRE/ΔFIRE mice, result in markedly reduced leukocyte recruitment. Supporting this, conditional microglial IL-1 deletion inhibits leukocyte recruitment. Unlike BAM depletion, the absence of microglia impairs hypercapnia-induced vasodilation, while in vivo two-photon imaging reveals microglial IL-1α-dependent interactions between leukocytes and penetrating arteries. Accordingly, reduced hypercapnia-induced vasodilation involves endothelial IL-1R1 and microglial IL-1α. Thus, distinct brain macrophage populations exert opposite effects on leukocyte recruitment and CBF through IL-1 dependent mechanisms in given vascular beds in male mice.
SN - 2041-1723
ER -