-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
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.1004262Souhrn
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
Článek Molecular and Cellular Mechanisms of KSHV Oncogenesis of Kaposi's Sarcoma Associated with HIV/AIDSČlánek Peptidoglycan Recognition Proteins Kill Bacteria by Inducing Oxidative, Thiol, and Metal Stress
Článok vyšiel v časopisePLOS Pathogens
Najčítanejšie tento týždeň
2014 Číslo 7- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
-
Všetky články tohto čísla
- Bacteriophages as Vehicles for Antibiotic Resistance Genes in the Environment
- Helminth Infections, Type-2 Immune Response, and Metabolic Syndrome
- Defensins and Viral Infection: Dispelling Common Misconceptions
- Holobiont–Holobiont Interactions: Redefining Host–Parasite Interactions
- The Wide World of Ribosomally Encoded Bacterial Peptides
- Microbial Egress: A Hitchhiker's Guide to Freedom
- Molecular and Cellular Mechanisms of KSHV Oncogenesis of Kaposi's Sarcoma Associated with HIV/AIDS
- HIV-1 Capture and Transmission by Dendritic Cells: The Role of Viral Glycolipids and the Cellular Receptor Siglec-1
- Tetherin Can Restrict Cell-Free and Cell-Cell Transmission of HIV from Primary Macrophages to T Cells
- The Frustrated Host Response to Is Bypassed by MyD88-Dependent Translation of Pro-inflammatory Cytokines
- Larger Mammalian Body Size Leads to Lower Retroviral Activity
- The Semen Microbiome and Its Relationship with Local Immunology and Viral Load in HIV Infection
- Lytic Gene Expression Is Frequent in HSV-1 Latent Infection and Correlates with the Engagement of a Cell-Intrinsic Transcriptional Response
- Phase Variation of Poly-N-Acetylglucosamine Expression in
- A Screen of Mutants Reveals Important Roles for Dot/Icm Effectors and Host Autophagy in Vacuole Biogenesis
- Structure of the Trehalose-6-phosphate Phosphatase from Reveals Key Design Principles for Anthelmintic Drugs
- The Impact of Juvenile Coxsackievirus Infection on Cardiac Progenitor Cells and Postnatal Heart Development
- Vertical Transmission Selects for Reduced Virulence in a Plant Virus and for Increased Resistance in the Host
- Characterization of the Largest Effector Gene Cluster of
- Novel Drosophila Viruses Encode Host-Specific Suppressors of RNAi
- Pto Kinase Binds Two Domains of AvrPtoB and Its Proximity to the Effector E3 Ligase Determines if It Evades Degradation and Activates Plant Immunity
- Genetic Analysis of Tropism Using a Naturally Attenuated Cutaneous Strain
- Plasmacytoid Dendritic Cells Suppress HIV-1 Replication but Contribute to HIV-1 Induced Immunopathogenesis in Humanized Mice
- A Novel Mouse Model of Gastroenteritis Reveals Key Pro-inflammatory and Tissue Protective Roles for Toll-like Receptor Signaling during Infection
- Pathogenicity of Is Expressed by Regulating Metabolic Thresholds of the Host Macrophage
- BCKDH: The Missing Link in Apicomplexan Mitochondrial Metabolism Is Required for Full Virulence of and
- Independent Bottlenecks Characterize Colonization of Systemic Compartments and Gut Lymphoid Tissue by
- Peptidoglycan Recognition Proteins Kill Bacteria by Inducing Oxidative, Thiol, and Metal Stress
- G3BP1, G3BP2 and CAPRIN1 Are Required for Translation of Interferon Stimulated mRNAs and Are Targeted by a Dengue Virus Non-coding RNA
- Cytolethal Distending Toxins Require Components of the ER-Associated Degradation Pathway for Host Cell Entry
- The Machinery at Endoplasmic Reticulum-Plasma Membrane Contact Sites Contributes to Spatial Regulation of Multiple Effector Proteins
- Arabidopsis LIP5, a Positive Regulator of Multivesicular Body Biogenesis, Is a Critical Target of Pathogen-Responsive MAPK Cascade in Plant Basal Defense
- Plant Surface Cues Prime for Biotrophic Development
- Real-Time Imaging Reveals the Dynamics of Leukocyte Behaviour during Experimental Cerebral Malaria Pathogenesis
- The CD27L and CTP1L Endolysins Targeting Contain a Built-in Trigger and Release Factor
- cGMP and NHR Signaling Co-regulate Expression of Insulin-Like Peptides and Developmental Activation of Infective Larvae in
- Systemic Hematogenous Maintenance of Memory Inflation by MCMV Infection
- Strain-Specific Variation of the Decorin-Binding Adhesin DbpA Influences the Tissue Tropism of the Lyme Disease Spirochete
- Distinct Lipid A Moieties Contribute to Pathogen-Induced Site-Specific Vascular Inflammation
- Serovar Typhi Conceals the Invasion-Associated Type Three Secretion System from the Innate Immune System by Gene Regulation
- LANA Binds to Multiple Active Viral and Cellular Promoters and Associates with the H3K4Methyltransferase hSET1 Complex
- A Molecularly Cloned, Live-Attenuated Japanese Encephalitis Vaccine SA-14-2 Virus: A Conserved Single Amino Acid in the Hairpin of the Viral E Glycoprotein Determines Neurovirulence in Mice
- Illuminating Fungal Infections with Bioluminescence
- Comparative Genomics of Plant Fungal Pathogens: The - Paradigm
- Motility and Chemotaxis Mediate the Preferential Colonization of Gastric Injury Sites by
- Widespread Sequence Variations in VAMP1 across Vertebrates Suggest a Potential Selective Pressure from Botulinum Neurotoxins
- An Immunity-Triggering Effector from the Barley Smut Fungus Resides in an Ustilaginaceae-Specific Cluster Bearing Signs of Transposable Element-Assisted Evolution
- Establishment of Murine Gammaherpesvirus Latency in B Cells Is Not a Stochastic Event
- Oncogenic Herpesvirus KSHV Hijacks BMP-Smad1-Id Signaling to Promote Tumorigenesis
- Human APOBEC3 Induced Mutation of Human Immunodeficiency Virus Type-1 Contributes to Adaptation and Evolution in Natural Infection
- Innate Immune Responses and Rapid Control of Inflammation in African Green Monkeys Treated or Not with Interferon-Alpha during Primary SIVagm Infection
- Chitin-Degrading Protein CBP49 Is a Key Virulence Factor in American Foulbrood of Honey Bees
- Influenza A Virus Host Shutoff Disables Antiviral Stress-Induced Translation Arrest
- Nsp9 and Nsp10 Contribute to the Fatal Virulence of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Emerging in China
- Pulmonary Infection with Hypervirulent Mycobacteria Reveals a Crucial Role for the P2X7 Receptor in Aggressive Forms of Tuberculosis
- Syk Signaling in Dendritic Cells Orchestrates Innate Resistance to Systemic Fungal Infection
- A Repetitive DNA Element Regulates Expression of the Sialic Acid Binding Adhesin by a Rheostat-like Mechanism
- T-bet and Eomes Are Differentially Linked to the Exhausted Phenotype of CD8+ T Cells in HIV Infection
- Israeli Acute Paralysis Virus: Epidemiology, Pathogenesis and Implications for Honey Bee Health
- Influence of ND10 Components on Epigenetic Determinants of Early KSHV Latency Establishment
- Antibody to gp41 MPER Alters Functional Properties of HIV-1 Env without Complete Neutralization
- PLOS Pathogens
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- Molecular and Cellular Mechanisms of KSHV Oncogenesis of Kaposi's Sarcoma Associated with HIV/AIDS
- Holobiont–Holobiont Interactions: Redefining Host–Parasite Interactions
- BCKDH: The Missing Link in Apicomplexan Mitochondrial Metabolism Is Required for Full Virulence of and
- Helminth Infections, Type-2 Immune Response, and Metabolic Syndrome
Prihlásenie#ADS_BOTTOM_SCRIPTS#Zabudnuté hesloZadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
- Časopisy