Lactobacilli‐lactoferrin interplay in Chlamydia trachomatis infection

&NA; In the cervicovaginal microenvironment, lactobacilli are known to protect against genital infections and, amongst the host defence compounds, lactoferrin has recently acquired importance for its anti‐microbial and anti‐inflammatory properties. An abnormal genital microenvironment facilitates the acquisition of pathogens like Chlamydia trachomatis, the leading cause of bacterial sexually transmitted infections worldwide. The aim of our study is to investigate the effects of Lactobacillus crispatus, Lactobacillus brevis and bovine lactoferrin on chlamydial infection, in order to shed light on the complex interplay between host defence mechanisms and C. trachomatis. We have also evaluated the effect of these defence factors to modulate the chlamydia‐mediated inflammatory state. To this purpose, we have determined the infectivity and progeny production of C. trachomatis as well as interleukin‐8 and interleukin‐6 synthesis. The main result of our study is that the combination of L. brevis and bovine lactoferrin is the most effective in inhibiting the early phases (adhesion and invasion) of C. trachomatis infection of cervical epithelial cells and in decreasing the levels of both cytokines. In conclusion, the interaction between L. brevis and lactoferrin seems to play a role in the protection against C. trachomatis, reducing the infection and regulating the immunomodulatory activity, thus decreasing the risk of severe complications. &NA; Graphical Abstract Figure. One sentence summary: The interaction between Lactobacillus brevis and lactoferrin seems to play a role in the protection against Chlamydia trachomatis genital infection.

[1]  P. Valenti,et al.  Effect of bovine lactoferrin on Chlamydia trachomatis infection and inflammation. , 2017, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[2]  Ashley M. Sherrid,et al.  Conservation of extrusion as an exit mechanism for Chlamydia. , 2016, Pathogens and disease.

[3]  C. Foschi,et al.  A Case of Reactive Arthritis Associated With Lymphogranuloma Venereum Infection in a Woman. , 2016, Sexually transmitted diseases.

[4]  J. Hegemann,et al.  The Chlamydia trachomatis Ctad1 invasin exploits the human integrin β1 receptor for host cell entry , 2016, Cellular microbiology.

[5]  S. Ouburg,et al.  Effect of cytokine level variations in individuals on the progression and outcome of bacterial urogenital infections--a meta-analysis. , 2016, Pathogens and disease.

[6]  Marleen Temmerman,et al.  Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting , 2015, PloS one.

[7]  J. Hocking,et al.  Treatment challenges for urogenital and anorectal Chlamydia trachomatis , 2015, BMC Infectious Diseases.

[8]  A. Luster,et al.  Chemokine‐mediated immune responses in the female genital tract mucosa , 2015, Immunology and cell biology.

[9]  S. Lebeer,et al.  Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health , 2015, Front. Physiol..

[10]  R. Ragno,et al.  Effects of Mentha suaveolens Essential Oil on Chlamydia trachomatis , 2015, BioMed research international.

[11]  A. Kreuter,et al.  2013 European guideline on the management of lymphogranuloma venereum , 2015, Journal of the European Academy of Dermatology and Venereology : JEADV.

[12]  E. McLaughlin,et al.  The Role of the Immune Response in Chlamydia trachomatis Infection of the Male Genital Tract: A Double-Edged Sword , 2014, Front. Immunol..

[13]  G. Schiavoni,et al.  Effects of vaginal lactobacilli in Chlamydia trachomatis infection. , 2014, International journal of medical microbiology : IJMM.

[14]  P. Valenti,et al.  Lactoferrin differently modulates the inflammatory response in epithelial models mimicking human inflammatory and infectious diseases , 2014, BioMetals.

[15]  T. Rudel,et al.  Modulation of host signaling and cellular responses by Chlamydia , 2013, Cell Communication and Signaling.

[16]  J. Hegemann,et al.  Characterization of the Interaction between the Chlamydial Adhesin OmcB and the Human Host Cell , 2013, Journal of bacteriology.

[17]  L. Mosca,et al.  Vaginal microbiota and viral sexually transmitted diseases. , 2013, Annali di igiene : medicina preventiva e di comunita.

[18]  R. Bastidas,et al.  Chlamydial intracellular survival strategies. , 2013, Cold Spring Harbor perspectives in medicine.

[19]  R. Sessa,et al.  New Insights into Chlamydiae Persistence: An Energy Metabolism Strategy? , 2013, International journal of immunopathology and pharmacology.

[20]  I. Choroszy-Król,et al.  Characteristics of the Chlamydia trachomatis species - immunopathology and infections. , 2012, Advances in clinical and experimental medicine : official organ Wroclaw Medical University.

[21]  N. Balakrishna,et al.  Effectiveness of vaginal tablets containing lactobacilli versus pH tablets on vaginal health and inflammatory cytokines: a randomized, double-blind study , 2012, European Journal of Clinical Microbiology & Infectious Diseases.

[22]  J. Carette,et al.  Attachment of Chlamydia trachomatis L2 to host cells requires sulfation , 2012, Proceedings of the National Academy of Sciences.

[23]  G. Schiavoni,et al.  Analysis of gene expression in penicillin G induced persistence of Chlamydia pneumoniae. , 2012, Journal of biological regulators and homeostatic agents.

[24]  S. Morré,et al.  The first case record of a female patient with bubonic lymphogranuloma venereum (LGV), serovariant L2b , 2012, Sexually Transmitted Infections.

[25]  I. Mylonas.  Female genital Chlamydia trachomatis infection: where are we heading? , 2012, Archives of Gynecology and Obstetrics.

[26]  C. Bébéar,et al.  First case of Chlamydia trachomatis L2b proctitis in a woman. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[27]  R. Ness,et al.  The Role of Chlamydia trachomatis Polymorphic Membrane Proteins in Inflammation and Sequelae among Women with Pelvic Inflammatory Disease , 2011, Infectious diseases in obstetrics and gynecology.

[28]  A. Polimeni,et al.  Antiviral Properties of Lactoferrin—A Natural Immunity Molecule , 2011, Molecules.

[29]  M. O’Sullivan,et al.  Public health policies and management strategies for genital Chlamydia trachomatis infection , 2011, Risk management and healthcare policy.

[30]  Santosh K. Ghosh,et al.  Multiplex Immunoassay of Lower Genital Tract Mucosal Fluid from Women Attending an Urban STD Clinic Shows Broadly Increased IL1ß and Lactoferrin , 2011, PloS one.

[31]  P. Wyrick.  Chlamydia trachomatis persistence in vitro: an overview. , 2010, The Journal of infectious diseases.

[32]  L. Mosca,et al.  Effectiveness of Lactobacillus-containing vaginal tablets in the treatment of symptomatic bacterial vaginosis. , 2009, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[33]  Kerry R. Buchholz,et al.  The Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Pathway Induces the Inflammatory Factor Interleukin-8 following Chlamydia trachomatis Infection , 2007, Infection and Immunity.

[34]  T. Okai,et al.  Cervical inflammatory cytokines and other markers in the cervical mucus of pregnant women with lower genital tract infection , 2006, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[35]  P. Valenti,et al.  Lactoferrin: an important host defence against microbial and viral attack. , 2005, Cellular and molecular life sciences : CMLS.

[36]  Yasser M. Abdelrahman,et al.  The chlamydial developmental cycle. , 2005, FEMS microbiology reviews.

[37]  P. Wyrick,et al.  Pre-exposure of infected human endometrial epithelial cells to penicillin in vitro renders Chlamydia trachomatis refractory to azithromycin. , 2004, The Journal of antimicrobial chemotherapy.

[38]  R. Stephens.  The cellular paradigm of chlamydial pathogenesis. , 2003, Trends in microbiology.

[39]  P. Brigidi,et al.  Characterization and selection of vaginal Lactobacillus strains for the preparation of vaginal tablets , 2002, Journal of applied microbiology.

[40]  G. Thurnau,et al.  The preterm prediction study: cervical lactoferrin concentration, other markers of lower genital tract infection, and preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. , 2000, American journal of obstetrics and gynecology.

[41]  H. Saito,et al.  Lactoferrin and interleukin-6 interaction in amniotic infection. , 1998, Advances in experimental medicine and biology.

[42]  J. Raulston.  Response of Chlamydia trachomatis serovar E to iron restriction in vitro and evidence for iron-regulated chlamydial proteins , 1997, Infection and immunity.

[43]  M. Kagnoff,et al.  Secretion of proinflammatory cytokines by epithelial cells in response to Chlamydia infection suggests a central role for epithelial cells in chlamydial pathogenesis. , 1997, The Journal of clinical investigation.

[44]  P. Visca,et al.  INTERACTION BETWEEN LACTOFERRIN AND OVOTRANSFERRIN AND CANDIDA CELLS , 1986 .