Biology subjects

Ivanova, D. L.

Publications and source records attributed to Ivanova, D. L..

2 recordsLinked to original sources

bioRxiv2019

Anti-Asialo GM1 treatment during secondary Toxoplasma gondii infection is lethal and depletes T cells

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 naive (Tn) CD8+ T cells were positive for ASGM1. Anti-ASGM1 treatment during reinfection resulted in greater depletion of activated IFN{gamma}+, Granzyme B+, Tem and Tef than Tcm and Tn CD8+ T cells. Anti-ASGM1 also depleted IFN{gamma}+ CD4+ T cells. Recombinant IFN{gamma} supplementation prolonged survival of anti-ASGM1 treated mice, demonstrating that this antibody eliminated IFN{gamma}-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.

immunology↗

bioRxiv2019

The IL-12 and IL-23-Dependent NK Cell Response is Essential For Protective Immunity Against Secondary Toxoplasma gondii Infection.

Natural Killer (NK) cells can develop memory-like features and contribute to long-term immunity in mice and humans. NK cells are critical for protection against acute T. gondii infection. However, whether they contribute to long-term immunity in response to this parasite is unknown. We used a vaccine challenge model of parasite infection to address this question and to define the mechanism by which NK cells are activated during secondary parasite infection. We found NK cells were required for control of secondary infection. NK cells increased in number at the infection site, became cytotoxic and produced IFN{gamma}. Adoptive transfer and NK-cell fate mapping revealed that T. gondii-experienced NK cells were not intrinsically different from naive NK cells with respect to their long-term persistence and ability to protect. Thus, they did not develop memory-like characteristics. Instead, a cell-extrinsic mechanism may control protective NK-cell responses during secondary infection. To test the involvement of a cell-extrinsic mechanism, we used anti-IL-12p70 and IL-12p35-/- mice and found that the secondary NK-cell response was not fully dependent on IL-12. IL-23 depletion with anti-IL-23p19 in vivo significantly reduced the secondary NK-cell response, suggesting that both IL-12 and IL-23 were involved. Anti-IL-12p40 treatment, which blocks both IL-12 and IL-23, eliminated the protective secondary NK-cell response, supporting this hypothesis. Our results define a previously unknown protective role for NK cells during secondary T. gondii infection that is dependent on IL-12 and IL-23.

immunology↗