FcRn-mediated transport of IgG can either enhance or neutralize chlamydial infection (49.17)

Abstract

Abstract IgG is the dominant antibody in the female and male reproductive tracts (RT). Furthermore, the neonatal Fc receptor (FcRn) is expressed by epithelial cells in both these tissues. The acidic environment (pH 4.5-6.5) in the RT is optimal for FcRn uptake of IgG by epithelial cells, which suggests that IgG could either enhance or protect against infection by pathogens such as Chlamydia, depending on antibody specificity. We show that IgG is indeed internalized by reproductive tract epithelial cells in an FcRn and pH-dependent manner. Furthermore, IgG specific for the chlamydial major outer membrane protein (MOMP), expressed predominantly on the extracellular elementary body (EB) actually enhanced infection, whilst IgG specific for an antigen expressed during intracellular chlamydial replication (IncA) partially neutralized infection. Both enhancement (IgG-MOMP) and protection (IgG-IncA) were abrogated by knockdown of FcRn expression. Chlamydiae inhibit lysosomal activity to promote infection and the presence of intracellular IncA-IgG enhanced lysosomal activity in infected cells. IgA is also found in RT secretions as is the IgA transport molecule the polyimmunoglobulin receptor (PIgR). Unlike IgG, IgA-MOMP and IgA-IncA both neutralized chlamydial infection in a PIgR-dependent manner. Thus for antibody-mediated protection against Chlamydia, IgG specific for intracellular chlamydial antigens, together with IgA specific for both stages of the replicative cycle may be optimal.