Lacticaseibacillus rhamnosus CRL1505 Ameliorates Liver Injury and Inflammation in Poly(I:C)-Induced Acute Hepatitis

TL;DR

This study shows that Lacticaseibacillus rhamnosus CRL1505 reduces liver damage and inflammation in a mouse model of acute hepatitis.

Contribution

The study reveals that CRL1505's protective effects in liver inflammation do not require mucus-binding adhesion.

Findings

CRL1505 reduced proinflammatory cytokines and improved liver enzyme levels in mice with acute hepatitis.

The Δmbf mutant of CRL1505 provided similar protection as the wild-type strain, indicating adhesion is not necessary.

CRL1505 enhanced antiviral factors and regulatory cytokines like IL-10 and IL-27.

Abstract

Lacticaseibacillus rhamnosus CRL1505 enhances antiviral immunity at mucosal sites, but its capacity to modulate liver immune responses remains unclear. Therefore, this study evaluated whether this immunomodulatory bacterium protects against Toll-like receptor 3 (TLR3)-mediated acute hepatitis induced by poly(I:C), and whether this effect depends on mucosal adhesion. BALB/c mice received the wild-type CRL1505 strain or the Δmbf CRL1505 mutant lacking the mucus-binding factor gene prior to poly(I:C) challenge. Liver injury, serum transaminases, and hepatic expression of interferons (IFNs), antiviral factors, inflammatory mediators, and regulatory cytokines were evaluated 48 h later. Poly(I:C) challenge induced acute hepatitis characterized by increased ALT/AST levels, leukocyte infiltration, and elevated hepatic IFNs and proinflammatory cytokines. The CRL1505 strain administration significantly reduced TNF-α, IL-1β, and IL-6 while enhancing IFNs, antiviral factors, and the regulatory cytokines IL-10 and IL-27, resulting in improved transaminase levels and attenuated liver damage. Notably, the Δmbf CRL1505 mutant conferred protection comparable to the wild-type strain. These findings demonstrate that L. rhamnosus CRL1505 exerts immunomodulatory and hepatoprotective effects during TLR3-driven hepatitis and that mbf-mediated adhesion is not required for this protection. Overall, CRL1505 emerges as a promising preventive strategy to enhance antiviral defenses and limit inflammation-associated liver injury.

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