Mathieu Deygas, Mathilde Bernard, Pierre Nivoit, Henry De Belly, Alexandre Deslys, Theresa Jakuszeit, Damien Cuvelier, Moira Garcia-Gomez, Lucie Barbier, Li Wang, Mathieu Maurin, Emmanuel Tejerina, Oumaima Baaziz, Emmanuel Terriac, Rafaele Attia, Anna Kniazeva, Serge Garbay, Marina Ortega-Zapero, Angela Saez, Raquel Gomez-Bris, Pilar Gonzalo, Jose M Gonzalez-Granado, Vicente Andrés, Orion D Weiner, Ana-Maria Lennon-Duménil, Guillaume Duménil, Matthieu Piel, Pablo Vargas
To reach inflamed tissues, neutrophils must traverse capillaries as narrow as 2 micrometers. However, how they do so without compromising blood flow or capillary function has remained unclear. By combining intravital live-cell imaging with biomimetic microdevices, we show that neutrophils maintain migration speed in capillaries across increasing levels of confinement. This behavior was not shared by other leukocytes and was independent of nuclear properties. Instead, confinement rapidly engaged Rho-dependent actomyosin contractility at the cell rear, thereby offsetting the increased mechanical resistance imposed by confinement. Disrupting this adaptive response caused neutrophil jamming and eventual occlusion of confined capillary-like networks. These findings identify a neutrophil-intrinsic mechanism that couples capillary confinement to rapid migratory adaptation, helping preserve vascular patency and potentially limiting tissue dysfunction during inflammation.