Ureaplasma parvum infection induces inflammatory changes in vaginal epithelial cells independent of sialidase.
Cytokines
Inflammation
Preterm birth
Sialidase
Ureaplasma parvum
Vaginal epithelial cells
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
received:
07
09
2022
accepted:
07
12
2022
medline:
29
3
2023
pubmed:
21
1
2023
entrez:
20
1
2023
Statut:
ppublish
Résumé
Ureaplasma, a genus of the order Mycoplasmatales and commonly grouped with Mycoplasma as genital mycoplasma is one of the most common microbes isolated from women with infection/inflammation-associated preterm labor (PTL). Mycoplasma spp. produce sialidase that cleaves sialic acid from glycans of vaginal mucous membranes and facilitates adherence and invasion of the epithelium by pathobionts, and dysregulated immune response. However, whether Ureaplasma species can induce the production of sialidase is yet to be demonstrated. We examined U. parvum-infected vaginal epithelial cells (VECs) for the production of sialidase and pro-inflammatory cytokines. Immortalized VECs were cultured in appropriate media and treated with U. parvum in a concentration of 1 × 10 Infection of VECs was confirmed by the presence of intracellular MBA. Western blot analysis showed no significant increase in sialidase expression from U. parvum-treated VECs compared to uninfected cells. However, U. parvum infection induced 2-3-fold increased production of GM-CSF (p = 0.03), IL-6 (p = 0.01), and IL-8 (p = 0.01) in VECs compared to controls. U. parvum infection of VECs induced inflammatory imbalance associated with vaginal dysbiosis but did not alter sialidase expression at the cellular level. These data suggest that U. parvum's pathogenic effect could be propagated by locally produced pro-inflammatory cytokines and, unlike other genital mycoplasmas, may be independent of sialidase.
Sections du résumé
BACKGROUND
BACKGROUND
Ureaplasma, a genus of the order Mycoplasmatales and commonly grouped with Mycoplasma as genital mycoplasma is one of the most common microbes isolated from women with infection/inflammation-associated preterm labor (PTL). Mycoplasma spp. produce sialidase that cleaves sialic acid from glycans of vaginal mucous membranes and facilitates adherence and invasion of the epithelium by pathobionts, and dysregulated immune response. However, whether Ureaplasma species can induce the production of sialidase is yet to be demonstrated. We examined U. parvum-infected vaginal epithelial cells (VECs) for the production of sialidase and pro-inflammatory cytokines.
METHODS
METHODS
Immortalized VECs were cultured in appropriate media and treated with U. parvum in a concentration of 1 × 10
RESULTS
RESULTS
Infection of VECs was confirmed by the presence of intracellular MBA. Western blot analysis showed no significant increase in sialidase expression from U. parvum-treated VECs compared to uninfected cells. However, U. parvum infection induced 2-3-fold increased production of GM-CSF (p = 0.03), IL-6 (p = 0.01), and IL-8 (p = 0.01) in VECs compared to controls.
CONCLUSION
CONCLUSIONS
U. parvum infection of VECs induced inflammatory imbalance associated with vaginal dysbiosis but did not alter sialidase expression at the cellular level. These data suggest that U. parvum's pathogenic effect could be propagated by locally produced pro-inflammatory cytokines and, unlike other genital mycoplasmas, may be independent of sialidase.
Identifiants
pubmed: 36662453
doi: 10.1007/s11033-022-08183-6
pii: 10.1007/s11033-022-08183-6
doi:
Substances chimiques
Neuraminidase
EC 3.2.1.18
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3035-3043Subventions
Organisme : Society for Reproductive investigation
ID : Society for Reproductive investigation
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Jefferson KK (2012) The bacterial etiology of preterm birth. Adv Appl Microbiol 80:1–22. https://doi.org/10.1016/b978-0-12-394381-1.00001-5
doi: 10.1016/b978-0-12-394381-1.00001-5
pubmed: 22794142
Amabebe E, Anumba DOC (2018) The Vaginal Microenvironment: the physiologic role of Lactobacilli. Front Med 5(181). https://doi.org/10.3389/fmed.2018.00181
Amabebe E, Anumba DOC (2022) Mechanistic insights into Immune suppression and evasion in bacterial vaginosis. Curr Microbiol 79(3):84. https://doi.org/10.1007/s00284-022-02771-2
doi: 10.1007/s00284-022-02771-2
pubmed: 35128579
pmcid: 8818625
Rumyantseva T, Khayrullina G, Guschin A, Donders G (2019) Prevalence of Ureaplasma spp. and Mycoplasma hominis in healthy women and patients with flora alterations. Diagn Microbiol Infect Dis 93(3):227–231. https://doi.org/10.1016/j.diagmicrobio.2018.10.001
doi: 10.1016/j.diagmicrobio.2018.10.001
pubmed: 30344067
Miyoshi Y, Suga S, Sugimi S, Kurata N, Yamashita H, Yasuhi I (2022) Vaginal Ureaplasma urealyticum or Mycoplasma hominis and preterm delivery in women with threatened preterm labor. J Maternal-Fetal Neonatal Med 35(5):878–883. https://doi.org/10.1080/14767058.2020.1733517
doi: 10.1080/14767058.2020.1733517
Cox C, Saxena N, Watt AP, Gannon C, McKenna JP, Fairley DJ et al (2016) The common vaginal commensal bacterium Ureaplasma parvum is associated with chorioamnionitis in extreme preterm labor. J Matern Fetal Neonatal Med 29(22):3646–3651. https://doi.org/10.3109/14767058.2016.1140734
doi: 10.3109/14767058.2016.1140734
pubmed: 26795404
Kataoka S, Yamada T, Chou K, Nishida R, Morikawa M, Minami M et al (2006) Association between preterm birth and vaginal colonization by mycoplasmas in early pregnancy. J Clin Microbiol 44(1):51–55. https://doi.org/10.1128/JCM.44.1.51-55.2006
doi: 10.1128/JCM.44.1.51-55.2006
pubmed: 16390947
pmcid: 1351938
Kacerovsky M, Kukla R, Bolehovska R, Bostik P, Matulova J, Mls J et al (2022) Prevalence and load of cervical Ureaplasma Species with respect to intra-amniotic complications in women with Preterm Prelabor rupture of membranes before 34 weeks. Front Pharmacol 13. https://doi.org/10.3389/fphar.2022.860498
Motomura K, Romero R, Xu Y, Theis KR, Galaz J, Winters AD et al (2020) Intra-amniotic infection with Ureaplasma parvum causes Preterm Birth and neonatal mortality that are prevented by treatment with clarithromycin. mBio 11(3):e00797–e00720. https://doi.org/10.1128/mBio.00797-20
doi: 10.1128/mBio.00797-20
pubmed: 32576673
pmcid: 7315120
Viscardi RM (2010) Ureaplasma species: role in diseases of prematurity. Clin Perinatol 37(2):393–409. https://doi.org/10.1016/j.clp.2009.12.003
doi: 10.1016/j.clp.2009.12.003
pubmed: 20569814
pmcid: 2891804
Sweeney EL, Dando SJ, Kallapur SG, Knox CL (2017) The human Ureaplasma species as causative agents of Chorioamnionitis. Clin Microbiol Rev 30(1):349–379. https://doi.org/10.1128/CMR.00091-16
doi: 10.1128/CMR.00091-16
pubmed: 27974410
Miralles R, Hodge R, McParland PC, Field DJ, Bell SC, Taylor DJ et al (2005) Relationship between antenatal inflammation and antenatal infection identified by detection of Microbial genes by polymerase chain reaction. Pediatr Res 57(4):570–577. https://doi.org/10.1203/01.PDR.0000155944.48195.97
doi: 10.1203/01.PDR.0000155944.48195.97
pubmed: 15695603
Yoon BH, Romero R, Kim M, Kim EC, Kim T, Park JS et al (2000) Clinical implications of detection of Ureaplasma urealyticum in the amniotic cavity with the polymerase chain reaction. Am J Obstet Gynecol 183(5):1130–1137. https://doi.org/10.1067/mob.2000.109036
doi: 10.1067/mob.2000.109036
pubmed: 11084554
Šket T, Ramuta T, Starčič Erjavec M, Kreft ME (2021) The role of Innate Immune System in the human amniotic membrane and human amniotic fluid in Protection against intra-amniotic infections and inflammation. Front Immunol 12. https://doi.org/10.3389/fimmu.2021.735324
Agarwal K, Lewis AL (2021) Vaginal sialoglycan foraging by Gardnerella vaginalis: mucus barriers as a meal for unwelcome guests? Glycobiology 31(6):667–680. https://doi.org/10.1093/glycob/cwab024
doi: 10.1093/glycob/cwab024
pubmed: 33825850
pmcid: 8252861
Lewis WG, Robinson LS, Gilbert NM, Perry JC, Lewis AL (2013) Degradation, foraging, and depletion of mucus sialoglycans by the vagina-adapted Actinobacterium Gardnerella vaginalis. J Biol Chem 288(17):12067–12079. https://doi.org/10.1074/jbc.M113.453654
doi: 10.1074/jbc.M113.453654
pubmed: 23479734
pmcid: 3636892
Smith DG, Russell WC, Thirkell D (1994) Adherence of Ureaplasma urealyticum to human epithelial cells. Microbiol (Reading) 140(Pt 10):2893–2898. https://doi.org/10.1099/00221287-140-10-2893
doi: 10.1099/00221287-140-10-2893
Castro J, Machado D, Cerca N (2019) Unveiling the role of Gardnerella vaginalis in polymicrobial bacterial vaginosis biofilms: the impact of other vaginal pathogens living as neighbors. ISME J 13(5):1306–1317. https://doi.org/10.1038/s41396-018-0337-0
doi: 10.1038/s41396-018-0337-0
pubmed: 30670827
pmcid: 6474217
Hardy L, Jespers V, Van den Bulck M, Buyze J, Mwambarangwe L, Musengamana V et al (2017) The presence of the putative Gardnerella vaginalis sialidase A gene in vaginal specimens is associated with bacterial vaginosis biofilm. PLoS ONE 12(2):e0172522. https://doi.org/10.1371/journal.pone.0172522
doi: 10.1371/journal.pone.0172522
pubmed: 28241058
pmcid: 5328246
Wiggins R, Hicks SJ, Soothill PW, Millar MR, Corfield AP (2001) Mucinases and sialidases: their role in the pathogenesis of sexually transmitted infections in the female genital tract. Sex Transm Infect 77(6):402–408. https://doi.org/10.1136/sti.77.6.402
doi: 10.1136/sti.77.6.402
pubmed: 11714935
pmcid: 1744407
Swidsinski A, Mendling W, Loening-Baucke V, Ladhoff A, Swidsinski S, Hale LP et al (2005) Adherent biofilms in bacterial vaginosis. Obstet Gynecol 106(5 Pt 1):1013–1023. https://doi.org/10.1097/01.AOG.0000183594.45524.d2
doi: 10.1097/01.AOG.0000183594.45524.d2
pubmed: 16260520
Swidsinski A, Mendling W, Loening-Baucke V, Swidsinski S, Dörffel Y, Scholze J et al (2008) An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole. Am J Obstet Gynecol 198(1):97e1–97e6. https://doi.org/10.1016/j.ajog.2007.06.039
doi: 10.1016/j.ajog.2007.06.039
Machado D, Castro J, Palmeira-de-Oliveira A, Martinez-de-Oliveira J, Cerca N (2015) Bacterial vaginosis Biofilms: challenges to current therapies and emerging solutions. Front Microbiol 6:1528. https://doi.org/10.3389/fmicb.2015.01528
doi: 10.3389/fmicb.2015.01528
pubmed: 26834706
Basavaprabhu HN, Sonu KS, Prabha R (2020) Mechanistic insights into the action of probiotics against bacterial vaginosis and its mediated preterm birth: an overview. Microb Pathog 141:104029. https://doi.org/10.1016/j.micpath.2020.104029
doi: 10.1016/j.micpath.2020.104029
pubmed: 32014462
Srinivasan U, Misra D, Marazita ML, Foxman B (2009) Vaginal and oral microbes, host genotype and preterm birth. Med Hypotheses 73(6):963–975. https://doi.org/10.1016/j.mehy.2009.06.017
doi: 10.1016/j.mehy.2009.06.017
pubmed: 19942083
pmcid: 4026093
Cauci S, Hitti J, Noonan C, Agnew K, Quadrifoglio F, Hillier SL et al (2002) Vaginal hydrolytic enzymes, immunoglobulin A against Gardnerella vaginalis toxin, and risk of early preterm birth among women in preterm labor with bacterial vaginosis or intermediate flora. Am J Obstet Gynecol 187(4):877–881. https://doi.org/10.1067/mob.2002.127454
doi: 10.1067/mob.2002.127454
pubmed: 12388968
Cauci S, Thorsen P, Schendel DE, Bremmelgaard A, Quadrifoglio F, Guaschino S (2003) Determination of immunoglobulin A against Gardnerella vaginalis hemolysin, sialidase, and prolidase activities in vaginal fluid: implications for adverse pregnancy outcomes. J Clin Microbiol 41(1):435–438. https://doi.org/10.1128/jcm.41.1.435-438.2003
doi: 10.1128/jcm.41.1.435-438.2003
pubmed: 12517887
pmcid: 149625
McGregor JA, French JI, Jones W, Milligan K, McKinney PJ, Patterson E et al (1994) Bacterial vaginosis is associated with prematurity and vaginal fluid mucinase and sialidase: results of a controlled trial of topical clindamycin cream. Am J Obstet Gynecol. ;170(4):1048-59; discussion 59–60. https://doi.org/10.1016/s0002-9378(94)70098-2
Robertson JA, Stemler ME, Stemke GW (1984) Immunoglobulin A protease activity of Ureaplasma urealyticum. J Clin Microbiol 19(2):255–258. https://doi.org/10.1128/jcm.19.2.255-258.1984
doi: 10.1128/jcm.19.2.255-258.1984
pubmed: 6365962
pmcid: 271032
Paralanov V, Lu J, Duffy LB, Crabb DM, Shrivastava S, Methé BA et al (2012) Comparative genome analysis of 19 Ureaplasma urealyticum and Ureaplasma parvumstrains. BMC Microbiol 12(1):88. https://doi.org/10.1186/1471-2180-12-88
doi: 10.1186/1471-2180-12-88
pubmed: 22646228
pmcid: 3511179
Kilian M, Brown MB, Brown TA, Freundt EA, Cassell GH (1984) Immunoglobulin A1 protease activity in strains of Ureaplasma urealyticum. Acta Pathologica Microbiologica Scandinavica Series B: Microbiology 92B(1–6):61–64. https://doi.org/10.1111/j.1699-0463.1984.tb02794.x
doi: 10.1111/j.1699-0463.1984.tb02794.x
Ligon JV, Kenny GE (1991) Virulence of ureaplasmal urease for mice. Infect Immun 59(3):1170–1171. https://doi.org/10.1128/iai.59.3.1170-1171.1991
doi: 10.1128/iai.59.3.1170-1171.1991
pubmed: 1997418
pmcid: 258383
Glass JI, Lefkowitz EJ, Glass JS, Heiner CR, Chen EY, Cassell GH (2000) The complete sequence of the mucosal pathogen Ureaplasma urealyticum. Nature 407(6805):757–762. https://doi.org/10.1038/35037619
doi: 10.1038/35037619
pubmed: 11048724
Herbst-Kralovetz MM, Quayle AJ, Ficarra M, Greene S, Rose WA 2, Chesson R et al (2008) Quantification and comparison of toll-like receptor expression and responsiveness in primary and immortalized human female lower genital tract epithelia. Am J Reprod Immunol 59(3):212–224. https://doi.org/10.1111/j.1600-0897.2007.00566.x
Tantengco OAG, Richardson L, Radnaa E, Kammala AK, Kechichian T, Ganguly E et al (2022) Cervix-on-a-chip for investigating ascending Ureaplasma parvum infection in pregnancy. Am J Obstet Gynecol 226(1):S12–S3. https://doi.org/10.1016/j.ajog.2021.11.068
doi: 10.1016/j.ajog.2021.11.068
Namba F, Hasegawa T, Nakayama M, Hamanaka T, Yamashita T, Nakahira K et al (2010) Placental features of Chorioamnionitis Colonized with Ureaplasma Species in Preterm Delivery. Pediatr Res 67(2):166–172. https://doi.org/10.1203/PDR.0b013e3181c6e58e
doi: 10.1203/PDR.0b013e3181c6e58e
pubmed: 19858776
Flori F, Secciani F, Capone A, Paccagnini E, Caruso S, Ricci MG et al (2007) Menstrual cycle-related sialidase activity of the female cervical mucus is associated with exosome-like vesicles. Fertil Steril 88(4 Suppl):1212–1219. https://doi.org/10.1016/j.fertnstert.2007.01.209
doi: 10.1016/j.fertnstert.2007.01.209
pubmed: 17562335
Paolini L, Orizio F, Busatto S, Radeghieri A, Bresciani R, Bergese P et al (2017) Exosomes secreted by HeLa cells shuttle on their Surface the plasma Membrane-Associated Sialidase NEU3. Biochemistry 56(48):6401–6408. https://doi.org/10.1021/acs.biochem.7b00665
doi: 10.1021/acs.biochem.7b00665
pubmed: 29039925
Cavanagh M, Amabebe E, Anumba DOC (2019) Differential Cytokine and Metabolite production by Cervicovaginal epithelial cells infected with Lactobacillus crispatus and Ureaplasma urealyticum. Anaerobe 102101. https://doi.org/10.1016/j.anaerobe.2019.102101
Uchida K, Nakahira K, Mimura K, Shimizu T, De Seta F, Wakimoto T et al (2013) Effects of Ureaplasma parvum lipoprotein multiple-banded antigen on pregnancy outcome in mice. J Reprod Immunol 100(2):118–127. https://doi.org/10.1016/j.jri.2013.10.001
doi: 10.1016/j.jri.2013.10.001
pubmed: 24238827
Zheng X, Teng LJ, Watson HL, Glass JI, Blanchard A, Cassell GH (1995) Small repeating units within the Ureaplasma urealyticum MB antigen gene encode serovar specificity and are associated with antigen size variation. Infect Immun 63(3):891–898. https://doi.org/10.1128/iai.63.3.891-898.1995
doi: 10.1128/iai.63.3.891-898.1995
pubmed: 7868260
pmcid: 173086
Shimizu T, Kida Y, Kuwano K (2008) Ureaplasma parvum lipoproteins, including MB antigen, activate NF-{kappa}B through TLR1, TLR2 and TLR6. Microbiol (Reading) 154(Pt 5):1318–1325. https://doi.org/10.1099/mic.0.2007/016212-0
doi: 10.1099/mic.0.2007/016212-0
Triantafilou M, De Glanville B, Aboklaish AF, Spiller OB, Kotecha S, Triantafilou K (2013) Synergic activation of toll-like receptor (TLR) 2/6 and 9 in response to Ureaplasma parvum & urealyticum in human amniotic epithelial cells. PLoS ONE 8(4):e61199. https://doi.org/10.1371/journal.pone.0061199
doi: 10.1371/journal.pone.0061199
pubmed: 23593431
pmcid: 3625198
Peltier MR, Freeman AJ, Mu HH, Cole BC (2007) Characterization of the macrophage-stimulating activity from Ureaplasma urealyticum. Am J Reprod Immunol 57(3):186–192. https://doi.org/10.1111/j.1600-0897.2006.00460.x
doi: 10.1111/j.1600-0897.2006.00460.x
pubmed: 17295897
Sweeney EL, Kallapur SG, Meawad S, Gisslen T, Stephenson S-A, Jobe AH et al (2017) Ureaplasma Species multiple banded Antigen (MBA) variation is Associated with the severity of inflammation in vivo and in vitro in Human Placentae. Front Cell Infect Microbiol 7:123. https://doi.org/10.3389/fcimb.2017.00123
doi: 10.3389/fcimb.2017.00123
pubmed: 28451522
pmcid: 5390016
Pavlidis I, Spiller OB, Sammut Demarco G, MacPherson H, Howie SEM, Norman JE et al (2020) Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice. Nat Commun 11(1):199. https://doi.org/10.1038/s41467-019-14089-y
doi: 10.1038/s41467-019-14089-y
pubmed: 31924800
pmcid: 6954262
Menon R, Behnia F, Polettini J, Richardson LS (2020) Novel pathways of inflammation in human fetal membranes associated with preterm birth and preterm pre-labor rupture of the membranes. Semin Immunopathol 42(4):431–450. https://doi.org/10.1007/s00281-020-00808-x
doi: 10.1007/s00281-020-00808-x
pubmed: 32785751
pmcid: 9296260
Noda-Nicolau NM, Tantengco OAG, Polettini J, Silva MC, Bento GFC, Cursino GC et al (2022) Genital mycoplasmas and biomarkers of inflammation and their Association with spontaneous Preterm Birth and Preterm Prelabor rupture of membranes: a systematic review and Meta-analysis. Front Microbiol 13:859732. https://doi.org/10.3389/fmicb.2022.859732
doi: 10.3389/fmicb.2022.859732
pubmed: 35432251
pmcid: 9006060
Plummer EL, Vodstrcil LA, Bodiyabadu K, Murray GL, Doyle M, Latimer RL et al (2021) Are Mycoplasma hominis, Ureaplasma urealyticum and Ureaplasma parvum Associated with specific genital symptoms and clinical signs in Nonpregnant Women? Clin Infect Dis 73(4):659–668. https://doi.org/10.1093/cid/ciab061
doi: 10.1093/cid/ciab061
pubmed: 33502501
Cunha G, Bastos LB, Freitas SF, Cavalli RC, Quintana SM (2022) Genital mycoplasma infection and spontaneous preterm birth outcome: a prospective cohort study. BJOG 129(2):273–281. https://doi.org/10.1111/1471-0528.16949
doi: 10.1111/1471-0528.16949
pubmed: 34559945
Jonduo ME, Vallely LM, Wand H, Sweeney EL, Egli-Gany D, Kaldor J et al (2022) Adverse pregnancy and birth outcomes associated with Mycoplasma hominis, Ureaplasma urealyticum and Ureaplasma parvum: a systematic review and meta-analysis. BMJ Open 12(8):e062990. https://doi.org/10.1136/bmjopen-2022-062990
doi: 10.1136/bmjopen-2022-062990
pubmed: 36028274
pmcid: 9422885
Vornhagen J, Armistead B, Santana-Ufret V, Gendrin C, Merillat S, Coleman M et al (2018) Group B streptococcus exploits vaginal epithelial exfoliation for ascending infection. J Clin Invest 128(5):1985–1999. https://doi.org/10.1172/jci97043
doi: 10.1172/jci97043
pubmed: 29629904
pmcid: 5919824
Weed S, Armistead B, Coleman M, Liggit HD, Johnson B, Tsai J et al (2020) MicroRNA signature of epithelial-mesenchymal transition in Group B Streptococcal infection of the placental chorioamniotic membranes. J Infect Dis 222(10):1713–1722. https://doi.org/10.1093/infdis/jiaa280
doi: 10.1093/infdis/jiaa280
pubmed: 32453818
pmcid: 7751568