Dataset Information

Mononuclear phagocyte system in hepatitis C virus infection.

ABSTRACT: The mononuclear phagocyte system (MPS), which consists of monocytes, dendritic cells (DCs), and macrophages, plays a vital role in the innate immune defense against pathogens. Hepatitis C virus (HCV) is efficient in evading the host immunity, thereby facilitating its development into chronic infection. Chronic HCV infection is the leading cause of end-stage liver diseases, liver cirrhosis, and hepatocellular carcinoma. Acquired immune response was regarded as the key factor to eradicate HCV. However, innate immunity can regulate the acquired immune response. Innate immunity-derived cytokines shape the adaptive immunity by regulating T-cell differentiation, which determines the outcome of acute HCV infection. Inhibition of HCV-specific T-cell responses is one of the most important strategies for immune system evasion. It is meaningful to illustrate the role of innate immune response in HCV infection. With the MPS being the important factor in innate immunity, therefore, understanding the role of the MPS in HCV infection will shed light on the pathophysiology of chronic HCV infection. In this review, we outline the impact of HCV infection on the MPS and cytokine production. We discuss how HCV is detected by the MPS and describe the function and impairment of MPS components in HCV infection.

SUBMITTER: Yang Y

PROVIDER: S-EPMC6262249 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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Mononuclear phagocyte system in hepatitis C virus infection.

Yang Yu Y Tu Zheng-Kun ZK Liu Xing-Kai XK Zhang Ping P

World journal of gastroenterology 20181101 44

The mononuclear phagocyte system (MPS), which consists of monocytes, dendritic cells (DCs), and macrophages, plays a vital role in the innate immune defense against pathogens. Hepatitis C virus (HCV) is efficient in evading the host immunity, thereby facilitating its development into chronic infection. Chronic HCV infection is the leading cause of end-stage liver diseases, liver cirrhosis, and hepatocellular carcinoma. Acquired immune response was regarded as the key factor to eradicate HCV. How ...[more]

PMID: 30510371

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Project description:The gut represents a potential entry site for a wide range of pathogens including protozoa, bacteria, viruses, or fungi. Consequently, it is protected by one of the largest and most diversified population of immune cells of the body. Its surveillance requires the constant sampling of its encounters by dedicated sentinels composed of follicles and their associated epithelium located in specialized area. In the small intestine, Peyer's patches (PPs) are the most important of these mucosal immune response inductive sites. Through several mechanisms including transcytosis by specialized epithelial cells called M-cells, access to the gut lumen is facilitated in PPs. Although antigen sampling is critical to the initiation of the mucosal immune response, pathogens have evolved strategies to take advantage of this permissive gateway to enter the host and disseminate. It is, therefore, critical to decipher the mechanisms that underlie both host defense and pathogen subversive strategies in order to develop new mucosal-based therapeutic approaches. Whereas penetration of pathogens through M cells has been well described, their fate once they have reached the subepithelial dome (SED) remains less well understood. Nevertheless, it is clear that the mononuclear phagocyte system (MPS) plays a critical role in handling these pathogens. MPS members, including both dendritic cells and macrophages, are indeed strongly enriched in the SED, interact with M cells, and are necessary for antigen presentation to immune effector cells. This review focuses on recent advances, which have allowed distinguishing the different PP mononuclear phagocyte subsets. It gives an overview of their diversity, specificity, location, and functions. Interaction of PP phagocytes with the microbiota and the follicle-associated epithelium as well as PP infection studies are described in the light of these new criteria of PP phagocyte identification. Finally, known alterations affecting the different phagocyte subsets during PP stimulation or infection are discussed.

Project description:Rationale: Exosomes are emerging as a promising drug delivery carrier. However, rapid uptake of exosomes by the mononuclear phagocyte system (MPS) remains an obstacle for drug delivery into other targeted organs, including the heart. We hypothesized that prior blocking of uptake of exosomes by the MPS would improve their delivery to the targeted organs. Methods: Exosomes were isolated from the cell culture medium. Fluorescence-labeled exosomes were tracked in vitro and in vivo by fluorescence imaging. The expression of clathrin heavy chain (Cltc), cavolin1, Pak1 and Rhoa, known genes for endocytosis, were profiled in various cell lines and organs by qPCR. The knockdown efficiency of siRNA against Cltc was analyzed by Western blotting. Exosomecontrol and exosomeblocking were constructed by encapsulating isolated exosomes with siControl or siClathrin via electroporation, while exosometherapeutic was constructed by encapsulating isolated exosomes with miR-21a. Doxorubicin-induced cardiotoxicity model was used to verify the therapeutic efficiency of the exosome-based miR-21a delivery by echocardiography. Results: Exosomes were preferentially accumulated in the liver and spleen, mainly due to the presence of abundant macrophages. Besides the well-known phagocytic effect, efficient endocytosis also contributes to the uptake of exosomes by macrophages. Cltc was found to be highly expressed in the macrophages compared with other endocytosis-associated genes. Accordingly, knockdown of Cltc significantly decreased the uptake of exosomes by macrophages in vitro and in vivo. Moreover, prior injection of exosomeblocking strikingly improved the delivery efficiency of exosomes to organs other than spleen and liver. Consistently, compared with the direct injection of exosometherapeutic, prior injection of exosomeblocking produced a much better therapeutic effect on cardiac function in the doxorubicin-induced cardiotoxicity mouse model. Conclusions: Prior blocking of endocytosis of exosomes by macrophages with exosomeblocking successfully and efficiently improves the distribution of following exosometherapeutic in targeted organs, like the heart. The established two-step exosome delivery strategy (blocking the uptake of exosomes first followed by delivery of therapeutic exosomes) would be a promising method for gene therapy.

Dataset Information

Mononuclear phagocyte system in hepatitis C virus infection.

Publications

Mononuclear phagocyte system in hepatitis C virus infection.

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