Facets of Innate Immunity to Viral Infection

A key feature of the innate immune system is its capacity to detect invading pathogens and identify them as dangerous. A variety of pathogen sensors have been described, referred to as pattern recognition receptors, that are expressed by various cells types, including dendritic cells and macrophages. Triggering of these sensors initiates various antiviral programs and mobilizes antigen-specific adaptive immune responses that act to eliminate the invading pathogen. Toll-like receptors (TLR) are a class of pattern recognition receptors that recognize structurally conserved molecules derived from microbes. In the current issue of Viral Immunology, four articles discuss different aspects of the innate immune response to viral infection.

Astill and colleagues use TLRs as vaccine adjuvants in the development of a vaccine against low pathogenic avian influenza virus infection in chickens. They specifically compare the adjuvanticity of TLR5 ligand (flagellin) and TLR21 ligand (CpG oligodeoxynucleotides) administered either alone or in combination with an intramuscular formaldehyde-inactivated H9N2 whole virus. Their data show that vaccines containing CpG oligodeoxynucleotides induce significantly greater systemic and lachrymal antibody responses than vaccines containing flagellin. However, combinations of flagellin and CpG oligodeoxynucleotides did not induce additive or synergistic effects on antibody-mediated immune responses. The authors suggest that future studies should examine the capacity of these adjuvants to induce cell-mediated immune responses.

In a second article, Chen et al. focus on various innate immune sensors for intracellular microbes in the context of acute and chronic hepatitis B virus (HBV) infection. Their data demonstrate that different immune sensors operate during acute versus chronic HBV infection and that some may contribute to HBV-induced immunotolerance. In a third article focused on innate immunity, Useche and colleagues have evaluated associations between single nucleotide polymorphisms (SNPs) in immune genes and the development of symptomatic dengue in children from Colombia. They identified SNPs associated with susceptibility or resistance to dengue fever in several innate immunity-related genes. These data advance our understanding of the genetic susceptibility/resistance to develop symptomatic dengue. A fourth article touches on innate immunity by focusing on interleukin-6 (IL-6), a pleiotropic cytokine that regulates immune and inflammatory responses. Naseem and colleagues have investigated the protective effect of IL-6 during chronic hepatitis C virus (HCV) infection using patient-derived peripheral blood mononuclear cells. The authors demonstrate that IL-6 promotes increased expression of antiapoptotic genes and downregulation of the T cell inhibitory receptor, TIM-3, suggesting a key role in enhancing lymphocyte effector function. The data suggest that IL-6 could be used as a potential candidate to improve adoptive T cell therapies for chronic HCV infection.

Two additional articles in this issue of Viral Immunology address other aspects of the immune response to viral infection. Hu et al. have investigated the role of microglia during pseudorabies virus (PRV) infection. The authors subcutaneously inoculated mice with different doses of a PRV vaccine strain and show that resting and activated microglia were observed in brain lesions. They further show that PRV can induce microglial proliferation and activation and that proliferating microglial cells originated from peripheral inflammatory monocytes. These data advance our understanding of the immunology of PRV infection. Finally, Aziz et al. have investigated the efficacy of a nucleoside reverse transcriptase inhibitor, tenofovir, at suppressing HBV DNA. The authors show that patients with a negative HBeAg (hepatitis B e-antigen, a viral protein that circulates in infected blood when the virus is actively replicating) profile exhibited a better virologic response than HBeAg-positive patients.

I would like to thank the authors for their excellent contributions to the Journal and all of the reviewers who work to ensure the high quality of published articles.