Organ system view of the hepatic innate immunity in HCV infection

Abstract

An orchestration of innate and adaptive immunity determines the infection outcome and whether the host achieves clearance or allows the pathogen to establish persistent infection. The robust activation of the innate immune response plays the most critical role in both limiting viral replication and halting the spread of the pathogen immediately after infection. The magnitude of innate immune activation is coupled with the efficient mounting of the adaptive immunity. Although immunity against HCV infection is known to be inadequate as most cases transitions to chronicity, approximately 25% of acute infection cases result in spontaneous clearance. The exact immune mechanisms that govern the infection outcome remain largely unknown; recent discoveries suggest that the innate immune system facilitates this event. Both infected hepatocytes and local innate immune cells trigger the front line defense program of the liver as well as the recruitment of diverse adaptive immune cells to the site of infection. Although hepatocyte is the target of HCV infection, nearly all cell types that exist in the liver are involved in the innate defense and contribute to the pathophysiology of hepatic inflammation. The main focus of this comprehensive review is to discuss the current knowledge on how each hepatic cell type contribute to the organ system level innate immunity against HCV infection as well as interplay with the viral evasion program. Furthermore, this review article also aims to synchronize the observations from both molecular biological studies and clinical studies with the ultimate goal of improving our understanding of HCV mediated hepatitis.

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

“…A similar process occurs in the liver of patients infected with dengue virus and yellow fever, where cytokines, such as TNF-α and TGF-β released by Kupffer cells, contribute to the development of a pro-inflammatory and proapoptotic environment in tissue hepatic necrosis, which leads to massive apoptosis of hepatocytes because of the proapoptotic action of TGF-β. 290,291 Viral influenza infections have been linked to lung injury induced by M1 macrophage-associated cytokines, including TNF-α, IFN-γ, and IL-6. Furthermore, these lung lesions might be attenuated in coinfection by Staphylococcus aureus, which is normally present in the airway mucosal microbiota, because of the bacterium's ability to stimulate the expression of M2 macrophages.…”

Detection of Occult Hepatitis C Virus Infection in Patients Who Achieved a Sustained Virologic Response to Direct-Acting Antiviral Agents for Recurrent Infection After Liver Transplantation

“…Given that HCV is a single-stranded (+) RNA virus, the detection of the negative (−) strand genome serves as a signature of HCV replication 3 . Subsequently, the liver and PBMC samples that were positive for OCI were subjected to a strand-specific RT-qPCR for the quantification of (+) and (−) strand HCV-genome.…”

Hepatitis C virus protein interaction network for HCV clearance and association of DAA to HCC occurrence via data mining approach: A systematic review and critical analysis

“…The molecular mechanisms underlying how HCV perturbs the cellular protein interaction networks may be attained within interpretative framework, which relies on entire biological process and pathways but not only on individual genes. Eradication of HCV infection involves coordinated effort between innate and adoptive immunity, as the innate immune responses initially, and later adaptive immunity becomes operational 8 weeks post‐infection . Initially, innate immunity recognises HCV via pattern recognition receptors (PRR) through TLRs, which target pathogen‐associated molecular patterns (PAMPs) found on HCV, thus augmenting immunity through upregulating IFN secretion and induction of IFN‐α‐inducible genes involved in antiviral and immune regulatory functions.…”

“…The molecular mechanisms underlying how HCV perturbs the cellular protein interaction networks may be attained within interpretative framework, which relies on entire biological process and pathways but not only on individual genes. Eradication of HCV infection involves coordinated effort between innate and adoptive immunity, as the innate immune responses initially, and later adaptive immunity becomes operational 8 weeks post-infection [28][29][30][31]. Initially, innate immunity recognises HCV via pattern recognition receptors (PRR)…”