| Autor: |
Lara R Mittereder, Jonathan Swoboda, Roberto De Pascalis, Karen L Elkins |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
PLoS ONE, Vol 18, Iss 3, p e0283161 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0283161 |
| Popis: |
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-γ 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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