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Brush border intermicrovillar adhesion limits bacterial attachment to the small intestine brush border

Cowell, R. P.; Bickart, A. C.; Shashi, S. R.; Vasquez, A.; Brackman, L. C.; Abdel-Dayem, M. A.; Chen, W.; Bowman, D. M.; Krystofiak, E. S.; Essalki, Y.; Gross, I.; Harrison, D. G.; Wanjalla, C. N.; Algood, H. M.; Tyska, M. J.; Meenderink, L. M.

2025-11-28 cell biology
10.1101/2025.11.25.690363 bioRxiv
Show abstract

Enterocytes present a continuous array of uniform, tightly packed, apical microvilli known as the "brush border". Adjacent microvilli tips are linked by an intermicrovillar adhesion complex (IMAC) composed of cadherins that are required for microvillar packing, length uniformity, and junctional integrity, with disruption linked to intestinal autoimmune disease and infections. We found that IMAC-deficient mice have dysbiosis with increased adherent (actin-dependent) and mucosal (actin-independent) bacteria in the terminal ileum. The bacteria are primarily commensals without differences in diversity between groups. Primary segments of Segmented filamentous bacteria (SFB) recruit the microvilli-associated proteins EPS8 and IRTKS, as well as the Arp2/3 complex, to remodel actin. SFB not only anchor adjacent to epithelial cell junctions but also incorporate ZO-1 into their attachment structures. Together, these data reveal maturation of the SFB-host interface that mirrors the complex SFB lifecycle. Our work indicates a previously unrecognized role for the brush border as a key component of host defense against luminal microbes.

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