Nasry Zane Bouzeineddine, Queen's University

Sebastien Talbot, Sam Basta and Katrina Gee. Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada, K7L 3N6

Fighting & Responding

The integrin CD103 is an adhesion molecule that facilitates immune cell retention in epithelial tissues through its interaction with E-cadherin. It is a defining marker for certain CD8 T cells subpopulations and conventional type 1 dendritic cells (cDC1), where they play a key role in antiviral immunity. While CD103 expression is well established in DCs and certain activated T cells, its presence in macrophages (MΦ) remains poorly characterized. Due to MΦ being early responders to viral infection, we investigated whether viral-associated inflammatory signals induce CD103 expression. Bone marrow-derived MΦ (BMDMs) were differentiated in M-CSF or GM-CSF and stimulated with endosomal Toll-like receptor (TLR) agonists that mimic viral nucleic acid sensing (TLR3, TLR7, and TLR9 ligands), or infected with virus. We found that CD103 is minimally expressed in BMDMs at baseline but is selectively upregulated in M-CSF-differentiated MΦ following stimulation with endosomal TLR agonists or following viral infection. Mechanistically, p38 MAPK inhibition prevented CD103 upregulation, indicating its role in regulating this process. Furthermore, in vivo LCMV infection induced CD103 expression on peritoneal macrophages. Our findings demonstrate that MΦ can acquire CD103 expression in response to viral stimuli in a differentiation-dependent manner. By showing that CD103 is not restricted to T cells and cDC1, this work revises the prevailing view of CD103 lineage specificity and identifies p38-dependent regulation of CD103 as a previously unrecognized component of MΦ activation during antiviral responses.