Abstract
Chlamydia trachomatis
is a major cause of sexually transmitted disease worldwide for which an effective vaccine is being actively pursued. Current vaccine efforts will be aided by elucidating the interaction between
Chlamydia
and dendritic cells (DCs). Protective immunity appears to develop slowly following natural infection in humans, and early vaccine trials using inactivated
C. trachomatis
resulted in partial, short-lived protection with possible enhanced inflammatory pathology during re-infection. Thus, immunity following natural infection with live chlamydia may differ fundamentally from immune responses induced by immunization with inactivated chlamydia. We explored this conjecture by studying the response of DCs exposed to either viable or inactivated [ultraviolet (UV) –irradiated] chlamydia elementary bodies (EBs; designated as Live-EB and UV-EB, respectively) using Affymetrix
GeneChip
microarrays. Thirty-one immunologically characterized genes were differentially expressed by DCs following exposure to Live-EB or UV-EB, including two glutamic acid–leucine–arginine cysteine–X–cysteine (ELR CXC) neutrophil chemoattractant chemokines,
Cxcl1
(KC), and
Cxcl2
(MIP-2). Up-regulation of these genes by Live-EB as compared to UV-EB was verified by quantitative reverse transcription–polymerase chain reaction and increased chemokine secretion was confirmed by enzyme-linked immunosorbent assay both
in vitro
and
in vivo
. Immunofluorescence and fluorescence-activated cell sorter analysis of chlamydia-infected lung tissue confirmed that Live-EB but not UV-EB induced significant DC and neutrophil infiltration during infection. These observations demonstrate that the development of an antichlamydial immune response is dramatically influenced by chlamydial viability. This has implications as to why early inactivated chlamydial vaccines were ineffective and suggests that new vaccine design efforts may benefit from
in vitro
DC screening for ELR chemokine expression profiles.