Pathogen recognition in the human female reproductive tract: expression of intracellular cytosolic sensors NOD1, NOD2, RIG-1, and MDA5 and response to HIV-1 and Neisseria gonorrhea.

PROBLEM: Expression patterns and regulation of cytosolic pattern recognition receptors (PRR) NOD-1, NOD-2, RIG-1, and MDA5 have not been elucidated in the human female reproductive tract (FRT).

METHOD OF STUDY: Primary epithelial cells (EC) isolated from Fallopian tube (FT), endometrium (EM), cervix (Cx), and ectocervix (Ecx) were treated with estradiol, poly(I:C), Neisseria gonorrhea (GC), and HIV-1. PRR mRNA expressions were analyzed by Real-time RT-PCR. Conditioned media were analyzed for IL-8 by ELISA.

RESULTS

EC from all FRT compartments constitutively expressed NOD1, NOD2, RIG-1, and MDA5 with highest levels expressed by FT. Stimulation with poly(I:C) resulted in upregulation of NOD2, RIG-1, and MDA5 in all FRT compartments and correlated with increased secretion of IL-8, whereas estradiol treatment had no effects. Exposure to GC and HIV-1 IIIB but not BaL resulted in selective upregulation of NOD2 and MDA5.

CONCLUSION

PRR are expressed throughout the FRT and differentially regulated by poly(I:C), GC and HIV-1.