Edinburgh Napier University

  Cationic Host Defense Peptides (CHDP), also known as antimicrobial peptides, are key components of the host innate immune response that have a wide range of direct microbicidal activities against a range of bacterial and viral pathogens, as well as a variety of immunomodulatory effects. CHDP are primarily expressed in tissues exposed to the external environment, and by cells of the innate immune system such as epithelial cells, macrophages, neutrophils and monocytes.
During pregnancy it is critical that the steroid milieu and the sterility of the reproductive tract are maintained for a successful pregnancy. In this study a mixture of ovine in vivo and in vitro steroid manipulations studies and an in vitro model of ovine placental infection are used. Using a fetal ovine animal model of dexamethasone and testosterone excess as models of compromised steroid milieu, we assessed the mRNA expression of the sheep cathelicidin SMAP-29 (Sheep Myeloid Antimicrobial Peptide-29) and sheep β-defensin 1 & 2 (sBD-1 and sBD-2) in the placenta, fetal thymus and fetal lung. These in vivo observations were followed up by in vitro steroid manipulation studies using the ovine trophoblast cell line AH-1 and the human lung epithelial cell line A549. Chlamydia abortus and Waddlia chondrophilia are both pathogens known to cause abortion in both livestock and humans. These pathogens were incubated with CHDP to determine their efficacy against such pathogens using an in vitro model of placental infection.
In vivo steroid manipulations resulted in significantly increased SMAP-29 levels in the fetal thymus of female sheep that were administered testosterone in utero. In vitro experiments found that the levels of SMAP-29, sBD1 and sBD2 were significantly altered by dexamethasone and only SMAP-29 was significantly altered by testosterone in the trophoblast cell line, AH-1.
The pre-incubation of C.abortus and W.chondrophilia with CHDP appears to aid organism growth, which is a novel observation for CHDP contributing to a potential role in pathogenicity. The proinflammatory profile of W.chondrophilia infection in the AH-1 cell line shows that the organism initiates an aggressive inflammatory response indicated by IL-8, IL-1β and TNFα expression. Waddlia infection also stimulates expression of sBD1 and sBD2 in the AH-1 cell line but, interestingly, not SMAP-29.
These data show how the steroid milieu and sterility, in the context of infection, of the reproductive tract can regulate the expression of CHDP, which could ultimately have an impact on the success of a pregnancy.