Abstract
The liver is a frontline immune site specifically designed to check and detect potential pathogens from the bloodstream to maintain a general state of immune hyporesponsiveness. One of the main functions of the liver is the regulation of iron homeostasis. The liver detects changes in systemic iron requirements and can regulate its concentration. Pathological states lead to the dysregulation of iron homeostasis which, in turn, can promote infectious and inflammatory processes. In this context, hepatic viruses deviate hepatocytes’ iron metabolism in order to better replicate. Indeed, some viruses are able to alter the expression of iron-related proteins or exploit host receptors to enter inside host cells. Lactoferrin (Lf), a multifunctional iron-binding glycoprotein belonging to the innate immunity, is endowed with potent antiviral activity, mainly related to its ability to block viral entry into host cells by interacting with viral and/or cell surface receptors. Moreover, Lf can act as an iron scavenger by both direct iron-chelation or the modulation of the main iron-related proteins. In this review, the complex interplay between viral hepatitis, iron homeostasis, and inflammation as well as the role of Lf are outlined.
Highlights
The liver contains the largest resident reticulo-endothelial cell network in the body, which composes the antigenic environment of the liver
A failure to initiate an appropriate immune response in the presence of viral infection or cancer can result in the development of chronic disease and organ failure
As much as 40% of men with perinatally acquired hepatitis B virus infection will die of liver cirrhosis or hepatocellular carcinoma
Summary
The liver represents the largest visceral organ in our body and an essential immunological organ, playing several crucial roles including detoxification, protein synthesis, and bile production [1]. Iron metabolism and homeostasis critically rely on the liver, being the major site for (i) the production of proteins that maintain systemic iron balance; (ii) the storage and mobilization of iron from hepatocytes to the circulation to meet metabolic requirements; (iii) iron recycling in conjunction with the spleen (splenic macrophages) [2]. Receiving both portal vein blood and arterial blood, the liver is a central component in the defense against blood-borne infections [3]. In the crosstalk between NK cells and KCs, TLR3 activation induces a higher IFN-γ response compared to TLR2 and TLR4, probably due to the induction of IL-12 without the presence of IL-10 coproduction [20]
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