Abstract Number: PB0760
Meeting: ISTH 2021 Congress
Background: Platelet-monocyte aggregate (PMA) formation contributes to thrombocytopenia in early HIV infection. PMAs mature into macrophages, and infected macrophages are an important barrier to cure. Canonically, monocyte P-selectin glycoprotein ligand 1 (PSGL-1) binds platelet P-selectin to form PMAs. In a non-infectious disease context, platelet binding to monocytes has further been shown to drive maturation of classical monocytes (CD14+ CD16-) into intermediate (CD14+ CD16+) and non-classical (CD14- CD16+) monocytes.
Aims: We utilized the EcoHIV mouse model of HIV to interrogate the importance of PSGL-1 in PMA formation as well as changes in surface marker expression of monocytes during infection.
Methods: Age-matched wild-type C57Bl/6J mice and PSGL-1 knockout mice were infected with EcoHIV or mock-infected with saline and euthanized at four endpoints (days 3, 9, 11, and 15 post-infection). Blood was collected via cardiac venipuncture and flow cytometry performed to interrogate PMA formation and monocyte maturation.
Results: In comparison to wild-type mice, PSGL-1 knockout mice formed significantly fewer PMAs (classical P<0.0001, intermediate P<0.0001, and non-classical monocytes P=0.007) throughout acute infection. Wild-type mice exhibited an increase in classical monocytes (Ly6C+ CD43-) with corresponding decrease in intermediate (Ly6C+ CD43+) and non-classical (Ly6C- CD43+) monocytes during acute infection, while PSGL-1 knockout mice instead demonstrated a large increase in intermediate monocytes (p<0.0001) with little to no change in classical (p<0.0001) and non-classical monocytes (p<0.0001).
Conclusions: We conclude that PSGL-1 is important for the formation of PMAs and the maturation of monocytes in the context of EcoHIV infection in mice, and that modulation of these interactions are an intriguing target for control of monocyte maturation in HIV.
To cite this abstract in AMA style:Lyons C, Shirk E, Vijay S, Feng A, Richardson MR, Gholizadeh Z, Carlson B, Guerrero-Martin S, Metcalf Pate K. PSGL-1 is Important for Platelet-monocyte Aggregate Formation and Monocyte Maturation in Lentiviral Infection [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/psgl-1-is-important-for-platelet-monocyte-aggregate-formation-and-monocyte-maturation-in-lentiviral-infection/. Accessed September 24, 2023.
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