The modulation of chlamydial replication by HLA-B27 depends on the cytoplasmic domain of HLA-B27.
OBJECTIVE
The intracellular persistence of viable Chlamydia trachomatis (CT) within the joint is thought to initiate and maintain the inflammatory process in CT-induced arthritis. CT-induced arthritis is associated with HLA-B27. Recently it was shown that HLA-B27, besides being a T-cell restriction element, can directly influence the invasion and/or replication of enterobacteriae and alters salmonella-induced signal transduction. It was the aim of this study to analyze the effect of HLA-B27 on CT-invasion and replication in human host cells.


METHODS
Human Hela cells and Hela cells transfected with either HLA-B27 cDNA or controls (HLA-A1 cDNA; HLA-B27 mutant = HLA-B27 without cytoplasmic tail; B27Q10 = HLA-B27 Exon 1-4 linked to Exon 5 of murine Q10) were infected with CT. By direct immunofluorescence chlamydial invasion was determined 4 hours post infection (p.i.), chlamydial replication 2 days and 4 days p.i. The number of infective CT in the different cell lines was determined by titration of the cell lysates on Hep-2 cells with subsequent immunoperoxidase staining.


RESULTS
Invasion was not affected by HLA-B27. However, formation of chlamydial inclusion bodies and replication was suppressed by HLA-B27. Genetically engineered mutants of HLA-B27 (HLA-B27 mutant, B27Q10) lacking the cytoplasmic tail of HLA-B27 did not affect replication.


CONCLUSIONS
The reduction of chlamydial replication by HLA-B27 depends on the cytoplasmic domain of HLA-B27, thus providing a new hypothesis for chlamydial persistence in HLA-B27 positive reactive arthritis.
Division of Rheumatology, Department of Internal Medicine, Hannover Medical School, Hannover, Germany. KUIPERS.JENS@MH-Hannover.DE
J G
JG
Kuipers
A
A
Bialowons
P
P
Dollmann
M C
MC
Jendro
L
L
Koehler
M
M
Ikeda
D T
DT
Yu
H
H
Zeidler
D002690:Chlamydia Infections / Q000382:microbiology*; D002692:Chlamydia trachomatis / Q000187:drug effects / Q000254:growth & development*; D015796:HLA-B27 Antigen / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells / Q000382:microbiology; D006801:Humans; D002479:Inclusion Bodies / Q000276:immunology / Q000382:microbiology*; D008856:Microscopy, Fluorescence / Q000379:methods; D017434:Protein Structure, Tertiary
D015796:HLA-B27 Antigen