| First Author | Morrow ZT | Year | 2023 |
| Journal | Infect Immun | Volume | 91 |
| Issue | 7 | Pages | e0054022 |
| PubMed ID | 37306593 | Mgi Jnum | J:351368 |
| Mgi Id | MGI:7663227 | Doi | 10.1128/iai.00540-22 |
| Citation | Morrow ZT, et al. (2023) Type I Interferon Signaling on Antigen-Presenting Cells Blunts Cell-Mediated Immunity toward Listeria monocytogenes. Infect Immun 91(7):e0054022 |
| abstractText | Listeria monocytogenes is a facultative intracellular pathogen that has been used for decades to understand mechanisms of bacterial pathogenesis and both innate and adaptive immunity. L. monocytogenes is a potent activator of CD8(+) T-cell-mediated immunity, yet how the innate immune response to infection modulates CD8(+) T-cell responses is incompletely understood. Here, we address how two innate immune pathways triggered by L. monocytogenes, type I interferon (IFN) production and inflammasome activation, impact the CD8(+) T-cell response. We utilized a combination of mutant mice and genetically engineered L. monocytogenes to address this question. Mice lacking the type I IFN receptor (IFNAR(-/-)) had the most robust T-cell response, while caspase-1(-/-) mice were not different from wild type (WT). Caspase-1(-/-)/IFNAR(-/-) mice had fewer T-cells than IFNAR(-/-) mice, suggesting a role for inflammasome activation in the absence of type I IFN. IFNAR(-/-) had more than twice as many memory precursors promoting enhanced protection from rechallenge. Importantly, short-lived effectors were equivalent in all strains of mice. L. monocytogenes strains genetically modified to induce lower type I interferon production yielded enhanced T-cell responses. IFNAR(-/-) dendritic cells induced more T-cells to proliferate than WT in ex vivo T-cell proliferation assays, suggesting deficits from type I interferon signaling may be dendritic cell intrinsic, rather than acting on T-cells. Thus, modulating type I IFN signaling during vaccination may lead to more potent T-cell-based vaccines. Importantly, this suggests innate immune signaling significantly impacts the CD8(+) T-cell response and suggests CD8(+) T-cell quantity and quality are important factors to consider during rational vaccine design. |
