Galectin-3 Deficiency Facilitates TNF-α-Dependent Hepatocyte Death and Liver Inflammation in MCMV Infection

• Published in: Frontiers in microbiology 2019-02, Vol.10, p.185-185
• Main Authors: Stojanovic, Bojana, Milovanovic, Jelena, Arsenijevic, Aleksandar, Stojanovic, Bojan, Strazic Geljic, Ivana, Arsenijevic, Nebojsa, Jonjic, Stipan, Lukic, Miodrag L, Milovanovic, Marija
• Format: Article
• Language: English
• Subjects: galectin-3; hepatitis; hepatocyte death; Microbiology; murine cytomegalovirus infection; TNF-α
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2019.00185

Galectin-3 (Gal-3) has a role in multiple inflammatory pathways. Various, opposite roles of Gal-3 in liver diseases have been described but there are no data about the role of Gal-3 in development of hepatitis induced with cytomegalovirus infection. In this study we aimed to clarify the role of Gal-3 in murine cytomegalovirus (MCMV)-induced hepatitis by using Gal-3-deficient (Gal-3 KO) mice. Here we provide the evidence that Gal-3 has the protective role in MCMV-induced hepatitis. Enhanced hepatitis manifested by more inflammatory and necrotic foci and serum level of ALT, enhanced apoptosis and necroptosis of hepatocytes and enhanced viral replication were detected in MCMV-infected Gal-3 deficient mice. NK cells does not contribute to more severe liver damage in MCMV-infected Gal-3 KO mice. Enhanced expression of TNF-α in the hepatocytes of Gal-3 KO mice after MCMV infection, abrogated hepatocyte death, and attenuated inflammation in the livers of Gal-3 KO mice after TNF-α blockade suggest that TNF-α plays the role in enhanced disease in Gal-3 deficient animals. Treatment with recombinant Gal-3 reduces inflammation and especially necrosis of hepatocytes in the livers of MCMV-infected Gal-3 KO mice. Our data highlight the protective role of Gal-3 in MCMV-induced hepatitis by attenuation of TNF-α-mediated death of hepatocytes.