| First Author | Nandi M | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 793918 | PubMed ID | 34956227 |
| Mgi Jnum | J:319367 | Mgi Id | MGI:6841579 |
| Doi | 10.3389/fimmu.2021.793918 | Citation | Nandi M, et al. (2021) IL-15Ralpha-Independent IL-15 Signaling in Non-NK Cell-Derived IFNgamma Driven Control of Listeria monocytogenes. Front Immunol 12:793918 |
| abstractText | Interleukin-15, produced by hematopoietic and parenchymal cells, maintains immune cell homeostasis and facilitates activation of lymphoid and myeloid cell subsets. IL-15 interacts with the ligand-binding receptor chain IL-15Ralpha during biosynthesis, and the IL-15:IL-15Ralpha complex is trans-presented to responder cells that express the IL-2/15Rbetagammac complex to initiate signaling. IL-15-deficient and IL-15Ralpha-deficient mice display similar alterations in immune cell subsets. Thus, the trimeric IL-15Ralphabetagammac complex is considered the functional IL-15 receptor. However, studies on the pathogenic role of IL-15 in inflammatory and autoimmune diseases indicate that IL-15 can signal independently of IL-15Ralpha via the IL-15Rbetagammac dimer. Here, we compared the ability of mice lacking IL-15 (no signaling) or IL-15Ralpha (partial/distinct signaling) to control Listeria monocytogenes infection. We show that IL-15-deficient mice succumb to infection whereas IL-15Ralpha-deficient mice clear the pathogen as efficiently as wildtype mice. IL-15-deficient macrophages did not show any defect in bacterial uptake or iNOS expression in vitro. In vivo, IL-15 deficiency impaired the accumulation of inflammatory monocytes in infected spleens without affecting chemokine and pro-inflammatory cytokine production. The inability of IL-15-deficient mice to clear L. monocytogenes results from impaired early IFNgamma production, which was not affected in IL-15Ralpha-deficient mice. Administration of IFNgamma partially enabled IL-15-deficient mice to control the infection. Bone marrow chimeras revealed that IL-15 needed for early bacterial control can originate from both hematopoietic and non-hematopoietic cells. Overall, our findings indicate that IL-15-dependent IL-15Ralpha-independent signaling via the IL-15Rbetagammac dimeric complex is necessary and sufficient for the induction of IFNgamma from sources other than NK/NKT cells to control bacterial pathogens. |
