Human β-defensin 2 plays a regulatory role in innate antiviral immunity and is capable of potentiating the induction of antigen-specific immunity

• Published in: Virology journal Vol. 15; no. 1; p. 124
• Main Authors: Kim, Ju, Yang, Ye Lin, Jang, Sun-Hee, Jang, Yong-Suk
• Format: Journal Article
• Language: English
• Published: England BioMed Central 08.08.2018; BMC
• Subjects: Adaptive immunity; Adaptive Immunity - immunology; Adjuvant; Adjuvants, Immunologic - administration & dosage; Animals; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Antibody; Antibody response; Antigen; Antigens; Antigens, Viral - chemistry; Antigens, Viral - immunology; Antimicrobial peptides; Antiviral Agents - immunology; beta-Defensins - chemistry; beta-Defensins - immunology; Cell Line, Tumor; Cercopithecus aethiops; Chemokines; Coronaviridae; Coronavirus Infections - immunology; Coronavirus Infections - prevention & control; Coronaviruses; Dendritic cells; Female; Human β-defensin; Humans; IL-1β; Immune system; Immunity, Innate - immunology; Immunization; Immunogenicity; Infections; Innate immunity; Interleukin 6; Laboratory animals; Leukocytes (granulocytic); Lymphocytes T; Macrophages; Macrophages - immunology; MERS-CoV; Mice; Mice, Inbred C57BL; Microorganisms; Middle East Respiratory Syndrome Coronavirus - chemistry; Middle East Respiratory Syndrome Coronavirus - immunology; Monocytes; Natural killer cells; NOD2 protein; Peptides; Proteins; Respiratory diseases; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - immunology; Spike protein; THP-1 Cells; Tumor necrosis factor-α; Vaccines; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - immunology; Vero Cells; Viral infections; Viral Vaccines - administration & dosage; Viral Vaccines - immunology; Viruses; β-Interferon; γ-Interferon; Antigen; Adjuvant; MERS-CoV; Antibody; Human β-defensin
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/s12985-018-1035-2

Antimicrobial peptides (AMPs) are primarily known for their innate immune defense against invading microorganisms, including viruses. In addition, recent research has suggested their modulatory activity in immune induction. Given that most subunit vaccines require an adjuvant to achieve effective immune induction through the activation of innate immunity, AMPs are plausible candidate molecules for stimulating not only innate immune but also adaptive immune responses. In this study, we investigated the ability of human β-defensin (HBD) 2 to promote antiviral immunity in vitro and in vivo using a receptor-binding domain (RBD) of Middle East respiratory syndrome-coronavirus (MERS-CoV) spike protein (S RBD) as a model antigen (Ag). When HBD 2-conjugated S RBD was used to treat THP-1 human monocytic cells, the expression levels of antiviral (IFN-β, IFN-γ, MxA, PKR, and RNaseL) and primary immune-inducing (NOD2, TNF-α, IL-1β, and IL-6) molecules were enhanced compared to those expressed after treatment with S RBD only. The expression of chemokines capable of recruiting leukocytes, including monocytes/macrophages, natural killer cells, granulocytes, T cells, and dendritic cells, was also increased following HBD 2-conjugated S RBD treatment. More important, immunization of mice with HBD 2-conjugated S RBD enhanced the immunogenicity of the S RBD and elicited a higher S RBD-specific neutralizing antibody response than S RBD alone. We conclude that HBD 2 activates the primary antiviral innate immune response and may also mediate the induction of an effective adaptive immune response against a conjugated Ag.