Vaginal Lactobacillus Inhibits HIV-1 Replication in Human Tissues Ex Vivo
Lactobacillus species, which dominate vaginal microbiota of healthy reproductive-age women, lower the risks of sexually transmitted infections, including the risk of human immunodeficiency virus (HIV) acquisition. The exact mechanisms of this protection remain to be understood. Here, we investigated...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-05-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fmicb.2017.00906/full |
| _version_ | 1818921509493669888 |
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| author | Rogers A. Ñahui Palomino Rogers A. Ñahui Palomino Sonia Zicari Christophe Vanpouille Beatrice Vitali Leonid Margolis |
| author_facet | Rogers A. Ñahui Palomino Rogers A. Ñahui Palomino Sonia Zicari Christophe Vanpouille Beatrice Vitali Leonid Margolis |
| author_sort | Rogers A. Ñahui Palomino |
| collection | DOAJ |
| description | Lactobacillus species, which dominate vaginal microbiota of healthy reproductive-age women, lower the risks of sexually transmitted infections, including the risk of human immunodeficiency virus (HIV) acquisition. The exact mechanisms of this protection remain to be understood. Here, we investigated these mechanisms in the context of human cervico-vaginal and lymphoid tissues ex vivo. We found that all six Lactobacillus strains tested in these systems significantly suppressed HIV type-1 (HIV-1) infection. We identified at least three factors that mediated this suppression: (i) Acidification of the medium. The pH of the undiluted medium conditioned by lactobacilli was between 3.8 and 4.6. Acidification of the culture medium with hydrochloric acid (HCl) to this pH in control experiments was sufficient to abrogate HIV-1 replication. However, the pH of the Lactobacillus-conditioned medium (CM) diluted fivefold, which reached ∼6.9, was also suppressive for HIV-1 infection, while in control experiments HIV-1 infection was not abrogated when the pH of the medium was brought to 6.9 through the use of HCl. This suggested the existence of other factors responsible for HIV-1 inhibition by lactobacilli. (ii) Lactic acid. There was a correlation between the concentration of lactic acid in the Lactobacillus-CM and its ability to suppress HIV-1 infection in human tissues ex vivo. Addition of lactic acid isomers D and L to tissue culture medium at the concentration that corresponded to their amount released by lactobacilli resulted in HIV-1 inhibition. Isomer L was produced in higher quantities than isomer D and was mostly responsible for HIV-1 inhibition. These results indicate that lactic acid, in particular its L-isomer, inhibits HIV-1 independently of lowering of the pH. (iii) Virucidal effect. Incubation of HIV-1 in Lactobacillus-CM significantly suppressed viral infectivity for human tissues ex vivo. Finally, lactobacilli adsorb HIV-1, serving as a sink decreasing the number of free virions. In summary, we found that lactobacilli inhibit HIV-1 replication in human tissue ex vivo by multiple mechanisms. Further studies are needed to evaluate the potential of altering the spectra of vaginal microbiota as an effective strategy to enhance vaginal health. Human tissues ex vivo may serve as a test system for these strategies. |
| first_indexed | 2024-12-20T01:38:47Z |
| format | Article |
| id | doaj.art-dd5a8cd1b5e646f885d0b27051b53078 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-20T01:38:47Z |
| publishDate | 2017-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-dd5a8cd1b5e646f885d0b27051b530782022-12-21T19:57:57ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2017-05-01810.3389/fmicb.2017.00906268627Vaginal Lactobacillus Inhibits HIV-1 Replication in Human Tissues Ex VivoRogers A. Ñahui Palomino0Rogers A. Ñahui Palomino1Sonia Zicari2Christophe Vanpouille3Beatrice Vitali4Leonid Margolis5Section of Intercellular Interaction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, BethesdaMD, United StatesDepartment of Pharmacy and Biotechnology, University of BolognaBologna, ItalySection of Intercellular Interaction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, BethesdaMD, United StatesSection of Intercellular Interaction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, BethesdaMD, United StatesDepartment of Pharmacy and Biotechnology, University of BolognaBologna, ItalySection of Intercellular Interaction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, BethesdaMD, United StatesLactobacillus species, which dominate vaginal microbiota of healthy reproductive-age women, lower the risks of sexually transmitted infections, including the risk of human immunodeficiency virus (HIV) acquisition. The exact mechanisms of this protection remain to be understood. Here, we investigated these mechanisms in the context of human cervico-vaginal and lymphoid tissues ex vivo. We found that all six Lactobacillus strains tested in these systems significantly suppressed HIV type-1 (HIV-1) infection. We identified at least three factors that mediated this suppression: (i) Acidification of the medium. The pH of the undiluted medium conditioned by lactobacilli was between 3.8 and 4.6. Acidification of the culture medium with hydrochloric acid (HCl) to this pH in control experiments was sufficient to abrogate HIV-1 replication. However, the pH of the Lactobacillus-conditioned medium (CM) diluted fivefold, which reached ∼6.9, was also suppressive for HIV-1 infection, while in control experiments HIV-1 infection was not abrogated when the pH of the medium was brought to 6.9 through the use of HCl. This suggested the existence of other factors responsible for HIV-1 inhibition by lactobacilli. (ii) Lactic acid. There was a correlation between the concentration of lactic acid in the Lactobacillus-CM and its ability to suppress HIV-1 infection in human tissues ex vivo. Addition of lactic acid isomers D and L to tissue culture medium at the concentration that corresponded to their amount released by lactobacilli resulted in HIV-1 inhibition. Isomer L was produced in higher quantities than isomer D and was mostly responsible for HIV-1 inhibition. These results indicate that lactic acid, in particular its L-isomer, inhibits HIV-1 independently of lowering of the pH. (iii) Virucidal effect. Incubation of HIV-1 in Lactobacillus-CM significantly suppressed viral infectivity for human tissues ex vivo. Finally, lactobacilli adsorb HIV-1, serving as a sink decreasing the number of free virions. In summary, we found that lactobacilli inhibit HIV-1 replication in human tissue ex vivo by multiple mechanisms. Further studies are needed to evaluate the potential of altering the spectra of vaginal microbiota as an effective strategy to enhance vaginal health. Human tissues ex vivo may serve as a test system for these strategies.http://journal.frontiersin.org/article/10.3389/fmicb.2017.00906/fullLactobacillusHIV-1human tissuelactic acidpH |
| spellingShingle | Rogers A. Ñahui Palomino Rogers A. Ñahui Palomino Sonia Zicari Christophe Vanpouille Beatrice Vitali Leonid Margolis Vaginal Lactobacillus Inhibits HIV-1 Replication in Human Tissues Ex Vivo Frontiers in Microbiology Lactobacillus HIV-1 human tissue lactic acid pH |
| title | Vaginal Lactobacillus Inhibits HIV-1 Replication in Human Tissues Ex Vivo |
| title_full | Vaginal Lactobacillus Inhibits HIV-1 Replication in Human Tissues Ex Vivo |
| title_fullStr | Vaginal Lactobacillus Inhibits HIV-1 Replication in Human Tissues Ex Vivo |
| title_full_unstemmed | Vaginal Lactobacillus Inhibits HIV-1 Replication in Human Tissues Ex Vivo |
| title_short | Vaginal Lactobacillus Inhibits HIV-1 Replication in Human Tissues Ex Vivo |
| title_sort | vaginal lactobacillus inhibits hiv 1 replication in human tissues ex vivo |
| topic | Lactobacillus HIV-1 human tissue lactic acid pH |
| url | http://journal.frontiersin.org/article/10.3389/fmicb.2017.00906/full |
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