Suppression of Antimicrobial Peptide Expression by Ureaplasma Species

Abstract

ABSTRACTUreaplasmaspecies commonly colonize the adult urogenital tract and are implicated in invasive diseases of adults and neonates. Factors that permit the organisms to cause chronic colonization or infection are poorly understood. We sought to investigate whether host innate immune responses, specifically, antimicrobial peptides (AMPs), are involved in determining the outcome ofUreaplasmainfections. THP-1 cells, a human monocytoid tumor line, were cocultured withUreaplasma parvumandU. urealyticum. Gene expression levels of a variety of host defense genes were quantified by real-time PCR.In vitroantimicrobial activities of synthetic AMPs againstUreaplasmaspp. were determined using a flow cytometry-based assay. Chromosomal histone modifications in host defense gene promoters were tested by chromatin immunoprecipitation (ChIP). DNA methylation status in the AMP promoter regions was also investigated. After stimulation withU. parvumandU. urealyticum, the expression of cell defense genes, including the AMP genes (DEFB1,DEFA5,DEFA6, andCAMP), was significantly downregulated compared to that ofTNFAandIL-8, which were upregulated.In vitroflow cytometry-based antimicrobial assay revealed that synthetic peptides LL-37, hBD-3, and hBD-1 had activity againstUreaplasmaspp. Downregulation of the AMP genes was associated with chromatin modification alterations, including the significantly decreased histone H3K9 acetylation withU. parvuminfection. No DNA methylation status changes were detected uponUreaplasmainfection. In conclusion, AMPs havein vitroactivity againstUreaplasmaspp., and suppression of AMP expression might be important for the organisms to avoid this aspect of the host innate immune response and to establish chronic infection and colonization.