DOCK2 Deficiency Causes Defects in Antiviral T-Cell Responses and Impaired Control of Herpes Simplex Virus Infection
Year: 2024
Type: article
Abstract: The expanding number of rare immunodeficiency syndromes offers an opportunity to understand key genes that support immune defense against infectious diseases. However, analysis of these in patients is complicated by their treatments and comorbid infections, requiring the use of mouse models for detailed investigations. We developed a mouse model of DOCK2 immunodeficiency and herein demonstrate that these mice have delayed clearance of herpes simplex virus type 1 (HSV-1) infections. We also uncovered a critical, cell-intrinsic role of DOCK2 in the priming of antiviral CD8+ T cells and in particular their initial expansion, despite apparently normal early activation of these cells. When this defect was overcome by priming in vitro, DOCK2-deficient CD8+ T cells were surprisingly protective against HSV-1 disease, albeit not as effectively as wild-type cells. These results shed light on a cellular deficiency that is likely to impact antiviral immunity in DOCK2-deficient patients.
Authors: Katrina L Randall, Inge E A Flesch, Yan Mei, Lisa A Miosge, Racheal Aye, Zhijia Yu, Heather Domaschenz, Natasha A Hollett, Tiffany A Russell, Tijana Stefanovic, Yik Chun Wong, Sandali Seneviratne, Fiona Ballard, Raquel Hernandez Gallardo, Sarah N Croft, Christopher C Goodnow, Edward M Bertram, Anselm Enders, David C Tscharke
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,001
Awards: Systems Approach to Immunity and Inflammation, The cellular basis of sex-specific responses to virus infection, Reducing the burden of DNA viruses on human health, A proteome-wide approach to anti-viral immunity and vaccine development, Modeling human Actin Related Protein 2/3 Complex subunit 1B (ARPC1B) deficiency in mice, G8104795072, G8397376588
OpenAlex ID: W4391898734