Extracellular matrix proteoglycans lumican and biglycan promote innate immune signals and viral clearance in HSV-1 infections of mouse corneas
- 1NYU Grossman School of Medicine
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.
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BibTeX
@misc{maiti2026extracellular,
title = {{Extracellular matrix proteoglycans lumican and biglycan promote innate immune signals and viral clearance in HSV-1 infections of mouse corneas}},
author = {G. Maiti and M. A. Koduri and E. Shin and Y. Shin and T. Sinha and A. Khodadadi-Jamayran and H. Yun and A. J. St. Leger and S. Chakravarti},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.15.751741},
url = {https://www.biorxiv.org/content/10.64898/2026.09.15.751741v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Extracellular matrix proteoglycans lumican and biglycan promote innate immune signals and viral clearance in HSV-1 infections of mouse corneas
AU - G. Maiti
AU - M. A. Koduri
AU - E. Shin
AU - Y. Shin
AU - T. Sinha
AU - A. Khodadadi-Jamayran
AU - H. Yun
AU - A. J. St. Leger
AU - S. Chakravarti
PY - 2026
DA - 2026/09/15
PB - bioRxiv
DO - 10.64898/2026.09.15.751741
UR - https://www.biorxiv.org/content/10.64898/2026.09.15.751741v1
AB - 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.
ER -