| First Author | Mittereder LR | Year | 2023 |
| Journal | PLoS One | Volume | 18 |
| Issue | 3 | Pages | e0283161 |
| PubMed ID | 36972230 | Mgi Jnum | J:334937 |
| Mgi Id | MGI:7450420 | Doi | 10.1371/journal.pone.0283161 |
| Citation | Mittereder LR, et al. (2023) IL-12p40 is essential but not sufficient for Francisella tularensis LVS clearance in chronically infected mice. PLoS One 18(3):e0283161 |
| abstractText | IL-12p40 plays an important role in F. tularensis Live Vaccine Strain (LVS) clearance that is independent of its functions as a part of the heterodimeric cytokines IL-12p70 or IL-23. In contrast to WT, p35, or p19 knockout (KO) mice, p40 KO mice infected with LVS develop a chronic infection that does not resolve. Here, we further evaluated the role of IL-12p40 in F. tularensis clearance. Despite reduced IFN-gamma production, primed splenocytes from p40 KO and p35 KO mice appeared functionally similar to those from WT mice during in vitro co-culture assays of intramacrophage bacterial growth control. Gene expression analysis revealed a subset of genes that were upregulated in re-stimulated WT and p35 KO splenocytes, but not p40 KO splenocytes, and thus are candidates for involvement in F. tularensis clearance. To directly evaluate a potential mechanism for p40 in F. tularensis clearance, we reconstituted protein levels in LVS-infected p40 KO mice using either intermittent injections of p40 homodimer (p80) or treatment with a p40-producing lentivirus construct. Although both delivery strategies yielded readily detectable levels of p40 in sera and spleens, neither treatment had a measurable impact on LVS clearance by p40 KO mice. Taken together, these studies demonstrate that clearance of F. tularensis infection depends on p40, but p40 monomers and/or dimers alone are not sufficient. |
