| First Author | De Pascalis R | Year | 2020 |
| Journal | PLoS One | Volume | 15 |
| Issue | 8 | Pages | e0237034 |
| PubMed ID | 32745117 | Mgi Jnum | J:293241 |
| Mgi Id | MGI:6450246 | Doi | 10.1371/journal.pone.0237034 |
| Citation | De Pascalis R, et al. (2020) Production of IFN-gamma by splenic dendritic cells during innate immune responses against Francisella tularensis LVS depends on MyD88, but not TLR2, TLR4, or TLR9. PLoS One 15(8):e0237034 |
| abstractText | Production of IFN-gamma is a key innate immune mechanism that limits replication of intracellular bacteria such as Francisella tularensis (Ft) until adaptive immune responses develop. Previously, we demonstrated that the host cell types responsible for IFN-gamma production in response to murine Francisella infection include not only natural killer (NK) and T cells, but also a variety of myeloid cells. However, production of IFN-gamma by mouse dendritic cells (DC) is controversial. Here, we directly demonstrated substantial production of IFN-gamma by DC, as well as hybrid NK-DC, from LVS-infected wild type C57BL/6 or Rag1 knockout mice. We demonstrated that the numbers of conventional DC producing IFN-gamma increased progressively over the course of 8 days of LVS infection. In contrast, the numbers of conventional NK cells producing IFN-gamma, which represented about 40% of non-B/T IFN-gamma-producing cells, peaked at day 4 after LVS infection and declined thereafter. This pattern was similar to that of hybrid NK-DC. To further confirm IFN-gamma production by infected cells, DC and neutrophils were sorted from naive and LVS-infected mice and analyzed for gene expression. Quantification of LVS by PCR revealed the presence of Ft DNA not only in macrophages, but also in highly purified, IFN-gamma producing DC and neutrophils. Finally, production of IFN-gamma by infected DC was confirmed by immunohistochemistry and confocal microscopy. Notably, IFN-gamma production patterns similar to those in wild type mice were observed in cells derived from LVS-infected TLR2, TLR4, and TLR2xTLR9 knockout (KO) mice, but not from MyD88 KO mice. Taken together, these studies demonstrate the pivotal roles of DC and MyD88 in IFN-gamma production and in initiating innate immune responses to this intracellular bacterium. |
