Extracellular matrix proteoglycans lumican and biglycan promote innate immune signals and viral clearance in HSV-1 infections of mouse corneas.

Authors

George Maiti, Madhuri A Koduri, Elizabeth Shin, Yoonchul Shin, Trisha Sinha, Alireza Khodadadi-Jamayran, Hongmin Yun, Anthony J St Leger, Shukti Chakravarti

Published in

bioRxiv : the preprint server for biology. Sep 18, 2026. Epub Sep 18, 2026.

Abstract

The extracellular matrix (ECM) regulates innate immunity, but its role in HSV-1 keratitis is unclear. Here, we identify the ECM proteoglycans lumican (Lum) and biglycan (Bgn) as key regulators of early antiviral defense in the cornea. Lum-/- and BgnKO mice showed impaired viral clearance, increased corneal opacity, and worse keratitis than wild-type controls. These defects were associated with reduced early recruitment of neutrophils, monocytes, and plasmacytoid dendritic cells, and blunted induction of pro-inflammatory cytokines, chemokines, and type I interferons. In infected wild-type corneas, Lum and Bgn were upregulated, including in the basal epithelium, where Ccl2 emerged as an early epithelial response that was diminished in knockout mice. In human corneal epithelial cells, recombinant LUM or BGN enhanced HSV-1-induced CCL2 secretion, and human corneal organoids recapitulated epithelial viral tropism and CCL2 induction. Together, these findings identify Lum and Bgn as regulators of epithelial-innate immune crosstalk that promote early antiviral immunity during corneal HSV-1 infection.

PMID:
42780025
Bibliographic data and abstract were imported from PubMed on 24 Sep 2026.

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