Abstract：
:Valproic acid (VPA) is a drug commonly used for epileptic seizure control. Recently, it has been shown that VPA alters the activation of several immune cells, including Natural Killer (NK) cells, which play an important role in the containment of viruses and intracellular bacteria. Although VPA can increase susceptibility to extracellular pathogens, it is unknown whether the suppressor effect of VPA could affect the course of intracellular bacterial infection. This study aimed to evaluate the role of VPA during Listeria monocytogenes (L.m) infection, and whether NK cell activation was affected. We found that VPA significantly augmented mortality in L.m infected mice. This effect was associated with increased bacterial load in the spleen, liver, and blood. Concurrently, decreased levels of IFN-γ in serum and lower splenic indexes were observed. Moreover, in vitro analysis showed that VPA treatment decreased the frequency of IFN-γ-producing NK cells within L.m infected splenocytes. Similarly, VPA inhibited the production of IFN-γ by NK cells stimulated with IL-12 and IL-18, which is a crucial system for early IFN-γ production in listeriosis. Finally, VPA decreased the phosphorylation of STAT4, p65, and p38, without affecting the expression of IL-12 and IL-18 receptors. Altogether, our results indicate that VPA increases the susceptibility to Listeria monocytogenes infection and suggest that NK cell is one of the main targets of VPA, but further work is needed to ascertain this effect.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Soria-Castro R,Chávez-Blanco AD,García-Pérez BE,Wong-Baeza I,Flores-Mejía R,Flores-Borja F,Estrada-Parra S,Estrada-García I,Serafín-López J,Chacón-Salinas Rdoi
10.1038/s41598-020-74836-wsubject
Has Abstractpub_date
2020-10-20 00:00:00pages
17802issue
1issn
2045-2322pii
10.1038/s41598-020-74836-wjournal_volume
10pub_type
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