Immunoglobulin A is an important mucosal antibody that can neutralize mucosal pathogens by either preventing attachment to epithelia (immune exclusion) or alternatively inhibit intra-epithelial replication following transcytosis by the
polymeric immunoglobulin receptor (pIgR). Chlamydia trachomatis is a major human pathogen that initially targets the endocervical or urethral epithelium in women and men, respectively. As both tissues contain abundant
secretory IgA (
SIgA) we assessed the protection afforded by
IgA targeting different chlamydial
antigens expressed during the extra- and intra-epithelial stages of
infection. We developed an in vitro model using polarizing cells expressing the murine pIgR together with
antigen-specific mouse
IgA, and an in vivo model using pIgR(-/-) mice.
Secretory IgA targeting the extra-epithelial chlamydial
antigen, the major outer
membrane protein, significantly reduced
infection in vitro by 24% and in vivo by 44%. Conversely, pIgR-mediated delivery of
IgA targeting the intra-epithelial inclusion
membrane protein A bound to the inclusion but did not reduce
infection in vitro or in vivo. Similarly, intra-epithelial
IgA targeting the secreted
protease Chlamydia
protease-like activity factor also failed to reduce
infection. Together, these data suggest the importance of pIgR-mediated delivery of
IgA targeting extra-epithelial, but not intra-epithelial, chlamydial
antigens for protection against a
genital tract infection.