CFTR is required for cellular entry and internalization of Chlamydia trachomatis.
Chlamydia trachomatis is an obligate intracellular Gram-negative pathogen affecting over 600 million people worldwide with 92 million new cases occurring globally each year. C. trachomatis enter the cells and replicate to infect different tissues/organs, giving rise to a spectrum of pathological conditions; however, the exact mechanism or receptor(s) for their entry is not well understood. Here we report that CFTR (cystic fibrosis transmembrane conductance regulator), an apical epithelial anion channel, is required for cellular entry and internalization of C. trachomatis. Human epithelial cell lines expressing functional CFTR internalized more C. trachomatis than the cells expressing mutant Delta508 CFTR. The in vitro cellular uptake of C. trachomatis can be blocked by CFTR inhibitors or antibody, and the in vivo cellular uptake of C. trachomatis in CFTR mutant (CFTR(-/-)) mice was significantly less compared with that in the wild-type. Direct interaction between CFTR and C. trachomatis LPS (lipopolysaccharide) is demonstrated by their immune-co-localization and co-immunoprecipitation. Despite an increase in CFTR expression observed upon C. trachomatis LPS challenge, a reduction in its ion channel activity is observed, consistent with the notion that CFTR functions as a receptor for cellular entry and internationization of C. trachomatis, with compromised ion-channel function. These findings, for the first time, demonstrate that CFTR functions as a cell-surface receptor for epithelial cell entry, and internalization of C. trachomatis and these findings may lead to the development of new treatment strategies to curtail the spread of chlamydial infections.
Ajonuma
Louis Chukwuemeka
LC
Epithelial Cell Biology Research Center, Department of Physiology, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, People's Republic of China.
Fok
Kin Lam
KL
Ho
Lok Sze
LS
Chan
Paul Kay Sheung
PK
Chow
Pak H
PH
Tsang
Lai Ling
LL
Wong
Connie Hau Yan
CH
Chen
Jie
J
Li
Shen
S
Rowlands
Dewi Kenneth
DK
Chung
Yiu Wa
YW
Chan
Hsiao Chang
HC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D002690:Chlamydia Infections / Q000378:metabolism / Q000382:microbiology*; D002692:Chlamydia trachomatis / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator