| First Author | Kupz A | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 13115 |
| PubMed ID | 32753607 | Mgi Jnum | J:299196 |
| Mgi Id | MGI:6457730 | Doi | 10.1038/s41598-020-70102-1 |
| Citation | Kupz A, et al. (2020) Treatment of mice with S4B6 IL-2 complex prevents lethal toxoplasmosis via IL-12- and IL-18-dependent interferon-gamma production by non-CD4 immune cells. Sci Rep 10(1):13115 |
| abstractText | Toxoplasmic encephalitis is an AIDS-defining condition. The decline of IFN-gamma-producing CD4(+) T cells in AIDS is a major contributing factor in reactivation of quiescent Toxoplasma gondii to an actively replicating stage of infection. Hence, it is important to characterize CD4-independent mechanisms that constrain acute T. gondii infection. We investigated the in vivo regulation of IFN-gamma production by CD8(+) T cells, DN T cells and NK cells in response to acute T. gondii infection. Our data show that processing of IFN-gamma by these non-CD4 cells is dependent on both IL-12 and IL-18 and the secretion of bioactive IL-18 in response to T. gondii requires the sensing of viable parasites by multiple redundant inflammasome sensors in multiple hematopoietic cell types. Importantly, our results show that expansion of CD8(+) T cells, DN T cells and NK cell by S4B6 IL-2 complex pre-treatment increases survival rates of mice infected with T. gondii and this is dependent on IL-12, IL-18 and IFN-gamma. Increased survival is accompanied by reduced pathology but is independent of expansion of TReg cells or parasite burden. This provides evidence for a protective role of IL2C-mediated expansion of non-CD4 cells and may represent a promising lead to adjunct therapy for acute toxoplasmosis. |
