Lactiplantibacillus plantarum CRL1506 ameliorates poly(I:C)-induced acute liver injury through cell wall-dependent modulation of inflammatory and antiviral immune responses.

Acute viral hepatitis is characterized by excessive inflammatory and antiviral immune responses that contribute to liver injury. Polyinosinic-polycytidylic acid [poly(I:C)], a synthetic analog of viral double-stranded RNA, is widely used to mimic virus-induced acute liver damage. Increasing evidence indicates that immunomodulatory probiotics (immunobiotics) can influence immune responses beyond the gut and exert beneficial effects in extraintestinal tissues like the liver. In this study, we evaluated the protective effects of Lactiplantibacillus plantarum CRL1506 and a surface-modified ΔdltD mutant strain in a murine model of poly(I:C)-induced acute liver injury. Oral administration of the wild-type CRL1506 strain significantly reduced serum transaminase levels and attenuated histopathological liver damage following a poly(I:C) challenge, whereas the mutant strain failed to confer protection. The protective effect induced by the CRL1506 strain was associated with a marked modulation of hepatic inflammatory mediators, including a reduction in proinflammatory cytokines, and improvements of antiviral factors and regulatory cytokines. This modulation of the liver cytokine profile was not achieved by the ΔdltD mutant strain, highlighting the role of lipoteichoic acid in the regulation of the immune system. Collectively, our findings demonstrate that L. plantarum CRL1506 confers protection against virus-like acute liver injury by fine-tuning inflammatory and antiviral immune pathways and highlight the relevance of bacterial surface configuration in mediating its immunobiotic and hepatoprotective effects. This study underlines the potential of immunobiotic strains as functional dietary interventions to mitigate acute liver inflammation triggered by viral components.