Effect of bovine lactoferrin onChlamydia trachomatisinfection and inflammation

Abstract

Chlamydia trachomatis is an obligate, intracellular pathogen responsible for the most common sexually transmitted bacterial disease worldwide, causing acute and chronic infections. The acute infection is susceptible to antibiotics, whereas the chronic one needs prolonged therapies, thus increasing the risk of developing antibiotic resistance. Novel alternative therapies are needed. The intracellular development of C. trachomatis requires essential nutrients, including iron. Iron-chelating drugs inhibit C. trachomatis developmental cycle. Lactoferrin (Lf), a pleiotropic iron binding glycoprotein, could be a promising candidate against C. trachomatis infection. Similarly to the efficacy against other intracellular pathogens, bovine Lf (bLf) could both interfere with C. trachomatis entry into epithelial cells and exert an anti-inflammatory activity. In vitro and in vivo effects of bLf against C. trachomatis infectious and inflammatory process has been investigated. BLf inhibits C. trachomatis entry into host cells when incubated with cell monolayers before or at the moment of the infection and down-regulates IL-6/IL-8 synthesized by infected cells. Six out of 7 pregnant women asymptomatically infected by C. trachomatis, after 30 days of bLf intravaginal administration, were negative for C. trachomatis and showed a decrease of cervical IL-6 levels. This is the first time that the bLf protective effect against C. trachomatis infection has been demonstrated.

Lactoferrin: A Natural Glycoprotein Involved in Iron and Inflammatory Homeostasis

“…This concept should be deeply reviewed in light of the capability of some bacteria to enter and survive inside cells, such as macrophages. Intracellular iron retention could be an inducer of the growth of facultative and obligate intracellular pathogens inside epithelial cells and macrophages, thus increasing infection severity [ 29 , 30 ]. In this respect, the recent discovery of the tight correlation between iron and inflammatory homeostasis must take into account that infectious processes by intracellular bacteria are favored and enhanced by intracellular iron overload, making imperative a strong revision of the classical iron therapy.…”

Diversity of Cervical Microbiota in Asymptomatic Chlamydia trachomatis Genital Infection: A Pilot Study

“…Recently, several studies have demonstrated the protective activity of vaginal Lactobacillus spp., as well as of other host defense factors present in the healthy cervico-vaginal micro-environment, toward C. trachomatis infection (Mastromarino et al, 2014; Nardini et al, 2016; Sessa et al, 2017a,b). Specifically, it has been showed that Lactobacillus crispatus and Lactobacillus brevis are able to interfere with the early phases of C. trachomatis infection as well as to inhibit its intracellular replication, preventing the dissemination of the infection in the host (Mastromarino et al, 2014; Sessa et al, 2017a).…”

Bacterial biota of women with bacterial vaginosis treated with lactoferrin: an open prospective randomized trial

“…All the women underwent a complete assessment in three scheduled appointments: at baseline (T0), on the 10th day of treatment (treatment: T1), and 2 weeks after the end of lactoferrin administration (post-treatment: T2). Inclusion criteria were sexually active women of reproductive age (18–45 years old) with regular menstrual cycles and with symptomatic acute BV diagnosed according to Amsel’s criteria [33] and Nugent score [34]. The exclusion criteria were age < 18 years; Nugent score < 7; known active infection due to Chlamydia , yeasts, Neisseria gonorrhoeae , or Trichomonas vaginalis ; clinically apparent herpes simplex infection or defined diagnosed human papillomavirus, herpes simplex virus type 2, or human immunodeficiency virus type 1 infection; pregnancy or breastfeeding; antibiotic, probiotic, or exogenous hormone treatments; and other gynecological conditions that could cause bleeding (polyps, endometrial hyperplasia, etc.).…”

“…Otsuki and Imai [33] showed that, in women with a history of multiple pregnancy losses or preterm delivery and refractory BV, lactoferrin administration could improve the vaginal microbiota, preventing both cervical inflammation and preterm delivery. Sessa et al [34] reported that intravaginal administration of lactoferrin resolved asymptomatic Chlamydia trachomatis in six out of seven pregnant women and resulted in normal deliveries.…”