Pregnancy Associates with Alterations to the Host and Microbial Proteome in Vaginal Mucosa

Overview

Journal Am J Reprod Immunol

Specialties Allergy & Immunology
Reproductive Medicine

Date 2020 Mar 21

PMID 32196803

Citations 5

Authors

Christina Farr Zuend

Nicole H Tobin

Trisha Vera

Lani Kotyrba

Laura Noel-Romas

Kenzie Birse

Sarah Mutch

Fan Li

David Lee

Stuart McCorrister

Garrett Westmacott

Grace M Aldrovandi

Adam D Burgener

Affiliations

Soon will be listed here.

Abstract

Problem: Pregnant women are at increased risk of HIV acquisition, but the biological mechanisms contributing to this observation are not well understood.

Method Of Study: Here, we assessed host immune and microbiome differences in the vaginal mucosa of healthy pregnant and non-pregnant women using a metaproteomics approach. Cervicovaginal lavage (CVL) samples were collected from 23 pregnant and 25 non-pregnant women.

Results: Mass spectrometry analysis of CVL identified 550 human proteins and 376 bacterial proteins from 11 genera. Host proteome analysis indicated 56 human proteins (10%) were differentially abundant (P < .05) between pregnant and non-pregnant women, including proteins involved in angiogenesis (P = 3.36E-3), cell movement of phagocytes (P = 1.34E-6), and permeability of blood vessels (P = 1.27E-4). The major bacterial genera identified were Lactobacillus, Gardnerella, Prevotella, Megasphaera, and Atopobium. Pregnant women had higher levels of Lactobacillus species (P = .017) compared with non-pregnant women. Functional pathway analysis indicated that pregnancy associated with changes to bacterial metabolic pathway involved in energy metabolism, which were increased in pregnant women (P = .035).

Conclusion: Overall, pregnant women showed differences in the cervicovaginal proteome and microbiome that may be important for HIV infection risk.

Citing Articles

Increased genital mucosal cytokines in Canadian women associate with higher antigen-presenting cells, inflammatory metabolites, epithelial barrier disruption, and the depletion of L. crispatus.

Farr Zuend C, Lamont A, Noel-Romas L, Knodel S, Birse K, Kratzer K Microbiome. 2023; 11(1):159.

PMID: 37491398 PMC: 10367425. DOI: 10.1186/s40168-023-01594-y.

Interactions between microbiota and cervical epithelial, immune, and mucus barrier.

Dong M, Dong Y, Bai J, Li H, Ma X, Li B Front Cell Infect Microbiol. 2023; 13:1124591.

PMID: 36909729 PMC: 9998931. DOI: 10.3389/fcimb.2023.1124591.

Utility of Proteomics in Emerging and Re-Emerging Infectious Diseases Caused by RNA Viruses.

Sperk M, van Domselaar R, Rodriguez J, Mikaeloff F, Vinhas B, Saccon E J Proteome Res. 2020; 19(11):4259-4274.

PMID: 33095583 PMC: 7640957. DOI: 10.1021/acs.jproteome.0c00380.

Microbiota and Human Reproduction: The Case of Female Infertility.

Tomaiuolo R, Veneruso I, Cariati F, DArgenio V High Throughput. 2020; 9(2).

PMID: 32375241 PMC: 7349014. DOI: 10.3390/ht9020012.

Pregnancy associates with alterations to the host and microbial proteome in vaginal mucosa.

Farr Zuend C, Tobin N, Vera T, Kotyrba L, Noel-Romas L, Birse K Am J Reprod Immunol. 2020; 83(6):e13235.

PMID: 32196803 PMC: 7317380. DOI: 10.1111/aji.13235.

References

Lamont R, Sobel J, Akins R, Hassan S, Chaiworapongsa T, Kusanovic J . The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG. 2011; 118(5):533-49. PMC: 3055920. DOI: 10.1111/j.1471-0528.2010.02840.x. View

Nagamatsu T, Schust D, Sugimoto J, Barrier B . Human decidual stromal cells suppress cytokine secretion by allogenic CD4+ T cells via PD-1 ligand interactions. Hum Reprod. 2009; 24(12):3160-71. DOI: 10.1093/humrep/dep308. View

H Gray R, Li X, Kigozi G, Serwadda D, Brahmbhatt H, Wabwire-Mangen F . Increased risk of incident HIV during pregnancy in Rakai, Uganda: a prospective study. Lancet. 2005; 366(9492):1182-8. DOI: 10.1016/S0140-6736(05)67481-8. View

Hughes B, Dutt R, Raker C, Barthelemy M, Rossoll R, Ramratnam B . The impact of pregnancy on anti-HIV activity of cervicovaginal secretions. Am J Obstet Gynecol. 2016; 215(6):748.e1-748.e12. PMC: 5124521. DOI: 10.1016/j.ajog.2016.06.057. View

Moss G, Clemetson D, Dcosta L, Plummer F, Ndinya-Achola J, Reilly M . Association of cervical ectopy with heterosexual transmission of human immunodeficiency virus: results of a study of couples in Nairobi, Kenya. J Infect Dis. 1991; 164(3):588-91. DOI: 10.1093/infdis/164.3.588. View

Alvarez-Olmos M, Barousse M, Rajan L, Van Der Pol B, Fortenberry D, Orr D . Vaginal lactobacilli in adolescents: presence and relationship to local and systemic immunity, and to bacterial vaginosis. Sex Transm Dis. 2004; 31(7):393-400. DOI: 10.1097/01.olq.0000130454.83883.e9. View

Klatt N, Cheu R, Birse K, Zevin A, Perner M, Noel-Romas L . Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women. Science. 2017; 356(6341):938-945. DOI: 10.1126/science.aai9383. View

Martin H, Richardson B, Nyange P, Lavreys L, Hillier S, Chohan B . Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis. 1999; 180(6):1863-8. DOI: 10.1086/315127. View

Reid S, Dai J, Wang J, Sichalwe B, Akpomiemie G, Cowan F . Pregnancy, contraceptive use, and HIV acquisition in HPTN 039: relevance for HIV prevention trials among African women. J Acquir Immune Defic Syndr. 2009; 53(5):606-13. PMC: 2845724. DOI: 10.1097/QAI.0b013e3181bc4869. View

10.

Taha T, Hoover D, Dallabetta G, Kumwenda N, MTIMAVALYE L, Yang L . Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV. AIDS. 1998; 12(13):1699-706. DOI: 10.1097/00002030-199813000-00019. View

11.

Lissauer D, Eldershaw S, Inman C, Coomarasamy A, Moss P, Kilby M . Progesterone promotes maternal-fetal tolerance by reducing human maternal T-cell polyfunctionality and inducing a specific cytokine profile. Eur J Immunol. 2015; 45(10):2858-72. PMC: 4833190. DOI: 10.1002/eji.201445404. View

12.

Walter J, Fraga L, Orin M, Decker W, Gipps T, Stek A . Immunomodulatory factors in cervicovaginal secretions from pregnant and non-pregnant women: a cross-sectional study. BMC Infect Dis. 2011; 11:263. PMC: 3190379. DOI: 10.1186/1471-2334-11-263. View

13.

Romero R, Hassan S, Gajer P, Tarca A, Fadrosh D, Nikita L . The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women. Microbiome. 2014; 2(1):4. PMC: 3916806. DOI: 10.1186/2049-2618-2-4. View

14.

Hyde K, Schust D . Immunologic challenges of human reproduction: an evolving story. Fertil Steril. 2016; 106(3):499-510. DOI: 10.1016/j.fertnstert.2016.07.1073. View

15.

Pendharkar S, Magopane T, Larsson P, de Bruyn G, Gray G, Hammarstrom L . Identification and characterisation of vaginal lactobacilli from South African women. BMC Infect Dis. 2013; 13:43. PMC: 3600991. DOI: 10.1186/1471-2334-13-43. View

16.

Keating M, Hamela G, Miller W, Moses A, Hoffman I, Hosseinipour M . High HIV incidence and sexual behavior change among pregnant women in Lilongwe, Malawi: implications for the risk of HIV acquisition. PLoS One. 2012; 7(6):e39109. PMC: 3387180. DOI: 10.1371/journal.pone.0039109. View

17.

Birse K, Arnold K, Novak R, McCorrister S, Shaw S, Westmacott G . Molecular Signatures of Immune Activation and Epithelial Barrier Remodeling Are Enhanced during the Luteal Phase of the Menstrual Cycle: Implications for HIV Susceptibility. J Virol. 2015; 89(17):8793-805. PMC: 4524071. DOI: 10.1128/JVI.00756-15. View

18.

Mbizvo M, Kasule J, Mahomed K, Nathoo K . HIV-1 seroconversion incidence following pregnancy and delivery among women seronegative at recruitment in Harare, Zimbabwe. Cent Afr J Med. 2002; 47(5):115-8. DOI: 10.4314/cajm.v47i5.8600. View

19.

Nagamatsu T, Schust D . The immunomodulatory roles of macrophages at the maternal-fetal interface. Reprod Sci. 2010; 17(3):209-18. DOI: 10.1177/1933719109349962. View

20.

Petrova M, Reid G, Vaneechoutte M, Lebeer S . Lactobacillus iners: Friend or Foe?. Trends Microbiol. 2016; 25(3):182-191. DOI: 10.1016/j.tim.2016.11.007. View