Transcriptional profiling reveals subset-specific cathepsin responses in cDC1 and cDC2 during ectromelia virus infection — ASN Events
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  3. Transcriptional profiling reveals subset-specific cathepsin responses in cDC1 and cDC2 during ectromelia virus infection

Transcriptional profiling reveals subset-specific cathepsin responses in cDC1 and cDC2 during ectromelia virus infection (#179)

Adrianna Niedzielska 1 , Michał Koper 2 , Karolina Gregorczyk-Zboroch 1 , Pola Pruchniak 1 , Małgorzata Gieryńska 1 , Felix N Toka 1 3 , Lidia Szulc-Dąbrowska 1
  1. Division of Immunology, Department of Preclinical Sciences, Warsaw University of Life Sciences, Warsaw, Poland
  2. Institute of Genetics and Biotechnology, University of Warsaw, Warsaw, mazowieckie, Poland
  3. One Health Center for Zoonoses and Tropical Infectious Diseases, Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis

Cathepsins are key regulators of antigen processing and innate immune signaling in dendritic cells (DCs). However, it remains unclear how comprehensive cathepsin expression profiles differ between conventional DC subsets (cDC1 and cDC2), and how these profiles change dynamically during viral infection in vivo. Here, we investigated the expression patterns of cathepsins in cDC1 and cDC2 in C57BL/6 mice infected with ectromelia virus (ECTV).

We performed RT-qPCR analysis of genes encoding cysteine, aspartyl, and serine cathepsins, and selected endogenous cystatin inhibitors in MACS-sorted splenic cDC1 and cDC2 from ECTV-infected mice at 5, 7, and 14 days post-infection (dpi).

Control cDC1 and cDC2 expressed all cathepsins; cDC1 showed high Ctsb/Ctsh/Ctss/Ctsz, moderate Ctsc/Ctsl/Ctso/Ctsd/Ctse, low Ctsf/Ctsk/Ctsw expression, while cDC2 showed similar expression, except for Ctsc, Ctsw and Ctsd , which were higher than in cDC1. In both cells, Ctsg was at the detection limit. ECTV infection induced a broader cathepsin response in cDC2 than in cDC1. In cDC2, genes for lysosomal cathepsins, particularly Ctsd and Ctsg, were strongly upregulated at 7 and 14 dpi. At 14 dpi, this response expanded to increased expression of Ctsb, Ctsl, Ctsc, Ctsw, and Ctse, showing broad activation of the proteolytic program in cDC2. In contrast, cDC1 exhibited a more restricted response, characterized mainly by increased Ctsg expression at 7 and 14 dpi and elevated Ctsd expression at 14 dpi. Cystatin gene expression was also subset- and time-dependent. cDC1 increased Cst7 expression at 5 and 7 dpi, while cDC2 showed early upregulation of Cst3 and Cstb at 5 dpi.

Our results demonstrate that ECTV infection differentially modulates cathepsin expression across DC subsets, with cDC2 displaying a broader proteolytic activation profile, while cDC1 responses remain more tightly controlled. These findings highlight distinct functional roles of DC subsets in antiviral immunity and identify cathepsins as potential regulators of DC-mediated immune responses.