Intravital pH Imaging using the sensor ApHID Reveals Incomplete Lysosomal Acidification in Resident Meningeal Phagocytes.
Abstract
Tracking lysosomes and quantifying their pH in the living, intact brain has been challenging owing to the lack of suitable in vivo tools. Here we report the use of dextran polymers labeled with the pH sensor ApHID to visualize and quantify lysosomal pH in mouse brain resident phagocytes. ApHID-dextrans delivered systemically are rapidly endocytosed by phagocytes in the meninges -mainly dural and subdural macrophages- and accumulate in lysosomal compartments. Intravital pH imaging revealed a striking heterogeneity in lysosomal acidification, with only ~5% of meningeal phagocytes reaching pH values below 5.0, in marked contrast with measurements in macrophage cell cultures. Photothrombotic ischemic lesions induced progressive lysosomal acidification in local phagocytes, while acute chloroquine treatment led to rapid alkalinization. Our methodology enables direct, quantitative pH measurements without genetic manipulations, and unveils a previously unappreciated heterogeneity in lysosomal acidification among brain-resident myeloid cells.
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BibTeX
@misc{soledomenech2026intravital,
title = {{Intravital pH Imaging using the sensor ApHID Reveals Incomplete Lysosomal Acidification in Resident Meningeal Phagocytes.}},
author = {S. Sole-Domenech and S. J. Ahn and M. Iskols and E. Capetillo-Zarate and L. Funes and J. Pedragosa Olle and C. Justicia Mercader and L.-M. Johnson and J. D. Warren and A. M. Planas and J. Anrather and C. Iadecola and F. R. Maxfield},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.12.750535},
url = {https://www.biorxiv.org/content/10.64898/2026.09.12.750535v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Intravital pH Imaging using the sensor ApHID Reveals Incomplete Lysosomal Acidification in Resident Meningeal Phagocytes.
AU - S. Sole-Domenech
AU - S. J. Ahn
AU - M. Iskols
AU - E. Capetillo-Zarate
AU - L. Funes
AU - J. Pedragosa Olle
AU - C. Justicia Mercader
AU - L.-M. Johnson
AU - J. D. Warren
AU - A. M. Planas
AU - J. Anrather
AU - C. Iadecola
AU - F. R. Maxfield
PY - 2026
DA - 2026/09/12
PB - bioRxiv
DO - 10.64898/2026.09.12.750535
UR - https://www.biorxiv.org/content/10.64898/2026.09.12.750535v1
AB - Tracking lysosomes and quantifying their pH in the living, intact brain has been challenging owing to the lack of suitable in vivo tools. Here we report the use of dextran polymers labeled with the pH sensor ApHID to visualize and quantify lysosomal pH in mouse brain resident phagocytes. ApHID-dextrans delivered systemically are rapidly endocytosed by phagocytes in the meninges -mainly dural and subdural macrophages- and accumulate in lysosomal compartments. Intravital pH imaging revealed a striking heterogeneity in lysosomal acidification, with only ~5% of meningeal phagocytes reaching pH values below 5.0, in marked contrast with measurements in macrophage cell cultures. Photothrombotic ischemic lesions induced progressive lysosomal acidification in local phagocytes, while acute chloroquine treatment led to rapid alkalinization. Our methodology enables direct, quantitative pH measurements without genetic manipulations, and unveils a previously unappreciated heterogeneity in lysosomal acidification among brain-resident myeloid cells.
ER -