Abstract
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.
Highlights
Infection with human cytomegalovirus (HCMV) is typically asymptomatic in immunocompetent individuals, but in individuals with immature or deficient immune system HCMV is a cause of morbidity and mortality (Mocarski et al, 2007)
Taking into account the facts that NK cells play a crucial role in the early immune response against murine cytomegalovirus (MCMV) in C57BL/6 mice (Scalzo and Yokoyama, 2008) and that NK cells contribute to liver damage in viral infections (Zheng et al, 2015), we explored the possibility that bigger liver damage in infected Gal3 KO mice is a consequence of stronger NK cell activity
We provide the first evidence that Gal-3 plays a protective role in MCMV-induced hepatitis as indicated by higher liver damage, serum levels of alanine transaminase (ALT) and higher virus titers in Gal3 deficient mice (Figure 2)
Summary
Infection with human cytomegalovirus (HCMV) is typically asymptomatic in immunocompetent individuals, but in individuals with immature or deficient immune system HCMV is a cause of morbidity and mortality (Mocarski et al, 2007). Murine CMV (MCMV) causes a chronic infection with initial hepatic inflammation and damage and is the most widely used model to study the pathogenesis of human CMV disease (Livingston-Rosanoff et al, 2012; Brune, 2013). TNF-α plays a role in defense against MCMV infection by activation of antiviral activities of T and NK cells (Orange and Biron, 1996), but is critical in MCMV-induced liver damage in normal or immunodeficient hosts (Orange et al, 1997). TNF-α-mediated signaling is required for the development of early necrotic foci in the livers of MCMV-infected C57BL/6J Rag-/- mice and the NK- and T- cell-deficient E26 mice, indicating that the main source of TNF-α are non-immune liver cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
