Data Sheet 1_CD160 mediated NK cell activation shapes host defense against acute Trypanosoma cruzi infection in the skin.pdf

While natural killer (NK) cell antimicrobial activity against T. cruzi-infected keratinocytes in the epidermis has previously been shown, NK cell interactions with dermal fibroblasts, a primary target of parasite replication at the skin entry site, remain poorly understood.</p>Methods<p>Bulk RNA-sequencing of mock- and T. cruzi-infected human dermal fibroblasts (HDF) and the BJ fibroblast cell line was performed to identify infection-induced ligand changes.

HVEM-CD160 binding and NK cell effector functions were assessed in vitro using fibroblast co-cultures with or without CD160 receptor blockade. In vivo, RAG^-/- and RAG^-/-CD160^-/- mice were infected intradermally with T. cruzi; NK cell degranulation and cytokine production were analyzed by flow cytometry, and parasite burden in skin and muscle was quantified by qPCR.</p>Results<p>RNA-sequencing revealed upregulation of herpesvirus entry mediator (HVEM, TNFRSF14) in infected human dermal fibroblasts, confirmed at the protein level.