The most common bacterial community in the genital tract among healthy
South African women not only is significantly different from that of
women in developed countries but also leads to elevated levels of
inflammatory proteins, which could increase the risk of HIV infection,
new research concludes.
"Ours is the first study to identify a specific bacterial community
in the genital tract of healthy women that is highly pro-inflammatory,
and we show this community is common in the women we studied in South
Africa," says Douglas Kwon, MD, PhD, of the Ragon Institute and the MGH
division of Infectious Diseases, senior author of the report. "We also
identified specific mechanisms by which the immune system senses these
bacterial species and potential mechanisms linking that response to
increased HIV susceptibility."
The authors note that, although inflammatory reactions in the female genital tract can prevent or eliminate many sexually transmitted infections, activation of the immune system paradoxically increases the risk that exposure to HIV will lead to infection. In the past, the bacterial population of the female tract was believed to be very simple and -- based on what was seen in white, premenopausal women -- dominated by a single Lactobacillus species. Since mild vaginal infections that alter the dominant microbial community can increase the risk of acquiring HIV and other sexually transmitted diseases, the researchers designed the current study to investigate whether differences in the genital microbial communities of healthy women might affect overall susceptibility to infection.
Analysis of genital samples from a group of 94 young black South African women -- who were HIV negative and had no disease symptoms -- revealed that only a minority had the sort of Lactobacillus-dominant bacterial communities commonly seen in U.S. women. The researchers grouped the samples they studied into four community types -- what they called cervicotypes -- based on the dominant bacterial species. The most common cervicotype among the study participants was very diverse, with low levels of Lactobacillus and no single dominant bacterial group.
To assess levels of immune activation in the study participants, the researchers measured levels of the immune system signaling molecules called cytokines in vaginal fluid samples and found significant individual differences -- as much as 1,000-fold in some cases. Elevated cytokines were not associated with active sexually transmitted infections or with factors such as sexual frequency or the use of condoms or hormonal contraceptives. Comparing cytokine levels among the cervicotypes revealed that the low-Lactobacillus, high-diversity communities were more than four times as likely to have elevated genital inflammatory cytokines. In fact, the presence of community was a better predictor of inflammation than was the presence of sexually transmitted diseases or other vaginal infections.
The researchers found that women with the highest levels of genital inflammation also had elevated levels of CCR5+ CD4+ T cells, the cells that are infected by HIV, in their genital tracts. "It has been shown that having a higher frequency of these HIV target cells at the site of exposure increases the risk of infection," says study lead author Melis Anahtar, an MD/PhD candidate in the Harvard/MIT Division of Health Sciences and Technology. "It's possible that treatments targeting specific genital bacteria could improve the effectiveness of measures -- such as antiretroviral vaginal gels -- designed to prevent HIV infection. In addition, finding that women with elevated genital inflammation may be three times more likely to become HIV-infected suggests that generally targeting the genital microbial population may further reduce risk."
An assistant professor of Medicine at Harvard Medical School, Kwon adds, "Understanding the impact of differences in the genital microbial population could also have implications for pregnant women and their infants. Some of the pro-inflammatory species that we found in our study were originally found in infected amniotic fluid and may contribute to the risk for premature birth and other complications of pregnancy." The research team is now investigating the specific mechanisms by which the immune system senses the presence of specific bacterial species in the female genital tract as well as examining the potential role of the broader microbial population, including viruses and fungi.
The authors note that, although inflammatory reactions in the female genital tract can prevent or eliminate many sexually transmitted infections, activation of the immune system paradoxically increases the risk that exposure to HIV will lead to infection. In the past, the bacterial population of the female tract was believed to be very simple and -- based on what was seen in white, premenopausal women -- dominated by a single Lactobacillus species. Since mild vaginal infections that alter the dominant microbial community can increase the risk of acquiring HIV and other sexually transmitted diseases, the researchers designed the current study to investigate whether differences in the genital microbial communities of healthy women might affect overall susceptibility to infection.
Analysis of genital samples from a group of 94 young black South African women -- who were HIV negative and had no disease symptoms -- revealed that only a minority had the sort of Lactobacillus-dominant bacterial communities commonly seen in U.S. women. The researchers grouped the samples they studied into four community types -- what they called cervicotypes -- based on the dominant bacterial species. The most common cervicotype among the study participants was very diverse, with low levels of Lactobacillus and no single dominant bacterial group.
To assess levels of immune activation in the study participants, the researchers measured levels of the immune system signaling molecules called cytokines in vaginal fluid samples and found significant individual differences -- as much as 1,000-fold in some cases. Elevated cytokines were not associated with active sexually transmitted infections or with factors such as sexual frequency or the use of condoms or hormonal contraceptives. Comparing cytokine levels among the cervicotypes revealed that the low-Lactobacillus, high-diversity communities were more than four times as likely to have elevated genital inflammatory cytokines. In fact, the presence of community was a better predictor of inflammation than was the presence of sexually transmitted diseases or other vaginal infections.
The researchers found that women with the highest levels of genital inflammation also had elevated levels of CCR5+ CD4+ T cells, the cells that are infected by HIV, in their genital tracts. "It has been shown that having a higher frequency of these HIV target cells at the site of exposure increases the risk of infection," says study lead author Melis Anahtar, an MD/PhD candidate in the Harvard/MIT Division of Health Sciences and Technology. "It's possible that treatments targeting specific genital bacteria could improve the effectiveness of measures -- such as antiretroviral vaginal gels -- designed to prevent HIV infection. In addition, finding that women with elevated genital inflammation may be three times more likely to become HIV-infected suggests that generally targeting the genital microbial population may further reduce risk."
An assistant professor of Medicine at Harvard Medical School, Kwon adds, "Understanding the impact of differences in the genital microbial population could also have implications for pregnant women and their infants. Some of the pro-inflammatory species that we found in our study were originally found in infected amniotic fluid and may contribute to the risk for premature birth and other complications of pregnancy." The research team is now investigating the specific mechanisms by which the immune system senses the presence of specific bacterial species in the female genital tract as well as examining the potential role of the broader microbial population, including viruses and fungi.
This story is taken from Science Daily
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