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The Semen Microbiome and Its Relationship with Local Immunology and Viral Load in HIV Infection


The classical paradigm of HIV infectivity centers on the blood HIV RNA viral load. However, while other fluid compartments such as semen and cerebrospinal fluid can have distinct viral loads from blood, the causes of localized HIV shedding are not fully understood. Since the semen viral load is an independent predictor of HIV transmission risk, it is critical to understand the local factors that trigger increased semen viral shedding in order to develop novel preventative strategies. Here, we evaluated the semen microbiome, bacterial load, and cytokine levels in 22 HIV-uninfected men who have sex with men (MSM) and in 27 HIV-infected MSM before and after initiation of antiretroviral therapy (ART). We found that HIV infection reduces semen microbiome biodiversity, which is restored with ART and immune reconstitution. We also found that semen bacterial load in untreated, HIV-infected men is associated with the levels of seven semen cytokines, relationships not seen in the uninfected controls. In particular, the cytokine IL-1b was uniquely correlated with both semen bacterial and viral load. Our findings support the interaction between semen microbiome and local immunology, and suggest that IL-1b could be a mechanism for semen microbiome to trigger semen viral shedding.


Vyšlo v časopise: The Semen Microbiome and Its Relationship with Local Immunology and Viral Load in HIV Infection. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004262
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004262

Souhrn

The classical paradigm of HIV infectivity centers on the blood HIV RNA viral load. However, while other fluid compartments such as semen and cerebrospinal fluid can have distinct viral loads from blood, the causes of localized HIV shedding are not fully understood. Since the semen viral load is an independent predictor of HIV transmission risk, it is critical to understand the local factors that trigger increased semen viral shedding in order to develop novel preventative strategies. Here, we evaluated the semen microbiome, bacterial load, and cytokine levels in 22 HIV-uninfected men who have sex with men (MSM) and in 27 HIV-infected MSM before and after initiation of antiretroviral therapy (ART). We found that HIV infection reduces semen microbiome biodiversity, which is restored with ART and immune reconstitution. We also found that semen bacterial load in untreated, HIV-infected men is associated with the levels of seven semen cytokines, relationships not seen in the uninfected controls. In particular, the cytokine IL-1b was uniquely correlated with both semen bacterial and viral load. Our findings support the interaction between semen microbiome and local immunology, and suggest that IL-1b could be a mechanism for semen microbiome to trigger semen viral shedding.


Zdroje

1. HladikF, McElrathMJ (2008) Setting the stage: host invasion by HIV. Nature reviews Immunology 8: 447–457.

2. KaulR, PettengellC, ShethPM, SunderjiS, BiringerA, et al. (2008) The genital tract immune milieu: an important determinant of HIV susceptibility and secondary transmission. Journal of reproductive immunology 77: 32–40.

3. BaetenJM, KahleE, LingappaJR, CoombsRW, Delany-MoretlweS, et al. (2011) Genital HIV-1 RNA predicts risk of heterosexual HIV-1 transmission. Science translational medicine 3: 77ra29.

4. ZhangH, DornadulaG, BeumontM, LivorneseLJr, Van UitertB, et al. (1998) Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretroviral therapy. The New England journal of medicine 339: 1803–1809.

5. CoombsRW, SpeckCE, HughesJP, LeeW, SampoleoR, et al. (1998) Association between culturable human immunodeficiency virus type 1 (HIV-1) in semen and HIV-1 RNA levels in semen and blood: evidence for compartmentalization of HIV-1 between semen and blood. The Journal of infectious diseases 177: 320–330.

6. ShethPM, YiTJ, KovacsC, KemalKS, JonesRB, et al. (2012) Mucosal correlates of isolated HIV semen shedding during effective antiretroviral therapy. Mucosal immunology 5: 248–257.

7. KalichmanSC, CageM, BarnettT, TharnishP, RompaD, et al. (2001) Human immunodeficiency virus in semen and plasma: investigation of sexual transmission risk behavioral correlates. AIDS research and human retroviruses 17: 1695–1703.

8. KalichmanSC, Di BertoG, EatonL (2008) Human immunodeficiency virus viral load in blood plasma and semen: review and implications of empirical findings. Sexually transmitted diseases 35: 55–60.

9. SpeckCE, CoombsRW, KoutskyLA, ZehJ, RossSO, et al. (1999) Risk factors for HIV-1 shedding in semen. American journal of epidemiology 150: 622–631.

10. GianellaS, StrainMC, RoughtSE, VargasMV, LittleSJ, et al. (2012) Associations between virologic and immunologic dynamics in blood and in the male genital tract. Journal of virology 86: 1307–1315.

11. GianellaS, SmithDM, VargasMV, LittleSJ, RichmanDD, et al. (2013) Shedding of HIV and Human Herpesviruses in the Semen of Effectively Treated HIV-1-Infected Men Who Have Sex With Men. Clin Infect Dis 57: 441–447.

12. WinterAJ, TaylorS, WorkmanJ, WhiteD, RossJD, et al. (1999) Asymptomatic urethritis and detection of HIV-1 RNA in seminal plasma. Sex Transm Infect 75: 261–263.

13. MalottRJ, KellerBO, GaudetRG, McCawSE, LaiCC, et al. (2013) Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression. Proceedings of the National Academy of Sciences of the United States of America 110: 10234–10239.

14. DingJ, RapistaA, TeleshovaN, MosoyanG, JarvisGA, et al. (2010) Neisseria gonorrhoeae enhances HIV-1 infection of primary resting CD4+ T cells through TLR2 activation. Journal of immunology 184: 2814–2824.

15. AndersonJA, PingLH, DibbenO, JabaraCB, ArneyL, et al. (2010) HIV-1 Populations in Semen Arise through Multiple Mechanisms. PLoS pathogens 6: e1001053.

16. VirecoulonF, WalletF, Fruchart-FlamenbaumA, RigotJM, PeersMC, et al. (2005) Bacterial flora of the low male genital tract in patients consulting for infertility. Andrologia 37: 160–165.

17. De FrancescoMA, NegriniR, RavizzolaG, GalliP, MancaN (2011) Bacterial species present in the lower male genital tract: a five-year retrospective study. The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception 16: 47–53.

18. LeterrierM, FreourT, GuillouzouicA, JuvinME, BarriereP, et al. (2011) Semen cultures analysis: retrospective study during a 6-year period and interest in the management of infertility. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 30: 401–406.

19. HouD, ZhouX, ZhongX, SettlesML, HerringJ, et al. (2013) Microbiota of the seminal fluid from healthy and infertile men. Fertility and Sterility 100: 1261–9.

20. PannekoekY, TrumJW, BlekerOP, van der VeenF, SpanjaardL, et al. (2000) Cytokine concentrations in seminal plasma from subfertile men are not indicative of the presence of Ureaplasma urealyticum or Mycoplasma hominis in the lower genital tract. J Med Microbiol 49: 697–700.

21. GdouraR, KchaouW, Ammar-KeskesL, ChakrounN, SellemiA, et al. (2008) Assessment of Chlamydia trachomatis, Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis, and Mycoplasma genitalium in semen and first void urine specimens of asymptomatic male partners of infertile couples. Journal of andrology 29: 198–206.

22. BorovkovaN, KorrovitsP, AusmeesK, TurkS, JoersK, et al. (2011) Influence of sexual intercourse on genital tract microbiota in infertile couples. Anaerobe 17: 414–418.

23. NelsonDE, DongQ, Van der PolB, TohE, FanB, et al. (2012) Bacterial communities of the coronal sulcus and distal urethra of adolescent males. PloS one 7: e36298.

24. DongQ, NelsonDE, TohE, DiaoL, GaoX, et al. (2011) The microbial communities in male first catch urine are highly similar to those in paired urethral swab specimens. PloS one 6: e19709.

25. LiuCM, HungateBA, TobianAA, SerwaddaD, RavelJ, et al. (2013) Male circumcision significantly reduces prevalence and load of genital anaerobic bacteria. mBio 4: e00076.

26. SalmeriM, ValentiD, La VigneraS, BellancaS, MorelloA, et al. (2012) Prevalence of Ureaplasma urealyticum and Mycoplasma hominis infection in unselected infertile men. J Chemother 24: 81–86.

27. ShethPM, KovacsC, KemalKS, JonesRB, RaboudJM, et al. (2009) Persistent HIV RNA shedding in semen despite effective antiretroviral therapy. AIDS 23: 2050–2054.

28. HuttenhowerC, GeversD, KnightR, AbubuckerS, BadgerJH, et al. (2012) Structure, function and diversity of the healthy human microbiome. Nature 486: 207–214.

29. CotillardA, KennedySP, KongLC, PriftiE, PonsN, et al. (2013) Dietary intervention impact on gut microbial gene richness. Nature 500: 585–588.

30. Le ChatelierE, NielsenT, QinJ, PriftiE, HildebrandF, et al. (2013) Richness of human gut microbiome correlates with metabolic markers. Nature 500: 541–546.

31. EronJJJr, SmeatonLM, FiscusSA, GulickRM, CurrierJS, et al. (2000) The effects of protease inhibitor therapy on human immunodeficiency virus type 1 levels in semen (AIDS clinical trials group protocol 850). The Journal of infectious diseases 181: 1622–1628.

32. SteklerJ, SycksBJ, HolteS, MaenzaJ, StevensCE, et al. (2008) HIV dynamics in seminal plasma during primary HIV infection. AIDS research and human retroviruses 24: 1269–1274.

33. OsborneBJW, ShethPM, KovacsC, MazzulliT, KaulR (2011) Impact of Collection Method on Assessment of Semen HIV RNA Viral Load. PloS one 6: e23654.

34. LiuCM, AzizM, KachurS, HsuehP-R, HuangY-T, et al. (2012) BactQuant: An enhanced broad-coverage bacterial quantitative real-time PCR assay. BMC Microbiology 12: 56.

35. Team RC (2013) R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing.

36. Oksanen J, Blanchet F, Kindt R, Legendre P, O'Hara R, et al.. (2011) vegan: Community Ecology Package. R package version 1.17–8.

37. SimpsonEH (1949) Measurement of Diversity. Nature 163: 688–688.

38. Roberts DW (2012) labdsv: Ordination and Multivariate Analysis for Ecology. R package version 1.5-0 ed.

39. Revelle W (2013) psych: Procedures for Personality and Psychological Research. Evanston, Illinois, US: Northwestern University.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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