Abstract
Using vaccine challenge model of T. gondii infection, we found that treatments with two commonly used for NK cell depletion antibodies resulted in different survival outcomes during secondary infection. Anti-ASGM1 resulted in 100% death and greater parasite burden at the site of infection than anti-NK1.1. Anti-NK1.1 treatment resulted in increased parasite burdens, but animals did not die. Further we found that anti-ASGM1 treatment depleted T cells. CD8+ T cells were more susceptible that CD4+ T cells to the treatment. ASGM1 was expressed on a higher percentage of CD8+ T cells than CD4+ T cells and CD8+ T cells. In T. gondii-immunized animals ASGM1 was enriched on effector memory (Tem) and central memory (Tcm) CD8+ T cells. However, Tem were more susceptible to the treatment. After secondary infection, Tem, Tcm, effector (Tef) and naïve (Tn) CD8+ T cells were positive for ASGM1. Anti-ASGM1 treatment during reinfection resulted in greater depletion of activated IFNγ+, Granzyme B+, Tem and Tef than Tcm and Tn CD8+ T cells. Anti-ASGM1 also depleted IFNγ+ CD4+ T cells. Recombinant IFNγ supplementation prolonged survival of anti-ASGM1 treated mice, demonstrating that this antibody eliminated IFNγ-producing T and NK cells important for control of the parasite. These results highlight that anti-ASGM1 antibody is not an optimal choice for targeting only NK cells and more precise approaches should be used. This study uncovers ASGM1 as a marker of activated effector T cells and the potential importance of changes in sialylation in lipid rafts for T cell activation during T. gondii infection.
Footnotes
This work is supported by grants from the American Heart Association AHA 17GRNT33700199 and University of Wyoming INBRE P20 GM103432 DRPP awarded to JPG. DLI is a University of Wyoming INBRE P20 GM103432 Graduate Assistantship recipient. SLD is a University of Wyoming INBRE P20 GM103432 supported undergraduate fellow. This project is supported in part by a grant from the National Institute of General Medical Sciences (2P20GM103432) from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health