Contribution of Fcγ Receptor-Mediated Immunity to the Pathogenesis Caused by the Human Respiratory Syncytial Virus

Front Cell Infect Microbiol. 2019 Mar 29:9:75. doi: 10.3389/fcimb.2019.00075. eCollection 2019.

Abstract

The human Respiratory Syncytial Virus (hRSV) is the leading cause of severe acute lower respiratory tract infections (ALRTIs) in humans at all ages and is the main cause of hospitalization due to pneumonia, asthma, and bronchiolitis in infants. hRSV symptoms mainly develop due to an excessive host immune and inflammatory response in the respiratory tissue. hRSV infection during life is frequent and likely because of non-optimal immunological memory is developed against this virus. Vaccine development against this pathogen has been delayed after the detrimental effects produced in children by vaccination with a formalin-inactivated hRSV preparation (FI-hRSV), which caused enhanced disease upon natural viral infection. Since then, several studies have focused on understanding the mechanisms underlying such disease exacerbation. Along these lines, several studies have suggested that antibodies elicited by immunization with FI-hRSV show low neutralizing capacity and promote the formation of immune complexes containing hRSV (hRSV-ICs), which contribute to hRSV pathogenesis through the engagement of Fc gamma receptors (FcγRs) expressed on the surface of immune cells. Furthermore, a role for FcγRs is supported by studies evaluating the contribution of these molecules to hRSV-induced disease. These studies have shown that FcγRs can modulate viral clearance by the host and the inflammatory response triggered by hRSV infection. In addition, ICs can facilitate viral entry into host cells expressing FcγRs, thus extending hRSV infectivity. In this article, we discuss current knowledge relative to the contribution of hRSV-ICs and FcγRs to the pathogenesis caused by hRSV and their putative role in the exacerbation of the disease caused by this virus after FI-hRSV vaccination. A better understanding FcγRs involvement in the immune response against hRSV will contribute to the development of new prophylactic or therapeutic tools to promote virus clearance with limited inflammatory damage to the airways.

Keywords: Fc gamma receptors; hRSV; immune complexes; inflammatory response; lung disease; opsonized virus; re-infection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigen-Antibody Complex / metabolism
  • Endocytosis
  • Host-Pathogen Interactions*
  • Humans
  • Receptors, IgG / metabolism*
  • Respiratory Syncytial Virus Infections / physiopathology*
  • Respiratory Syncytial Virus, Human / pathogenicity*

Substances

  • Antigen-Antibody Complex
  • Receptors, IgG