Nav: Home

Vaccination under the influence of estradiol increases vaginal antiviral immunity

May 05, 2016

When it comes to sexually transmitted infections (STIs), some female hormones are protective while others make women more susceptible. A study in mice published on May 5th in PLOS Pathogens suggests that estradiol (E2) exerts its protective effect against herpes virus by shifting the immune response in the vaginal mucosa toward a more effective antiviral one.

Many studies have shown that injectable contraceptives containing progestins may increase a woman's risk of being infected with HIV and with HSV-2, the virus causing genital herpes. On the other hand, estradiol, another hormone that is present during the normal menstrual cycle and contained in oral contraceptives, has been shown to be protective. To minimize unintended negative consequences of hormonal contraception, understanding how different hormones affect susceptibility to STI pathogens is important.

Charu Kaushic and colleagues from McMaster University in Hamilton, Canada, had previously shown that vaccination of mice against genital herpes (HSV-2) under the influence of estradiol leads to enhanced protection against the virus. In this study, the researchers examined the underlying mechanisms.

As in the earlier work, they implanted either E2-releasing pellets or control pellets into female mice whose ovaries (which normally produce both estradiol and progesterone) had been removed. The pellets release E2 for three weeks. Following implantation, the researchers exposed the mice to two rounds (2 weeks apart) of nasal HSV-2 vaccine, followed by a vaginal challenge with a high dose of intact HSV-2 virus 6 weeks later.

Most of the mice with the E2 pellets survived the challenge and showed much less severe disease symptoms. In contrast, most of the control mice got seriously sick and were euthanized. This was true for several different HSV vaccine formulations tested.

To examine the mechanism by which E2 enhanced immune protection in the HSV-2 vaccine model, the researchers studied immune cells and immune signaling molecules in the female genital tract following the HSV-2 challenge. They found that E2 treatment accelerates and increases the response of two types of T helper cells, namely Th1 and Th17 cells. (Th1 cells are required for host defense against intracellular viral and bacterial pathogens. Th17 cells are defined by their production of IL-17 and promote inflammation.)

Following viral challenge, cells of both types are recruited earlier and at larger numbers to the vaginal mucosa in mice that were vaccinated under E2 influence. Searching for the local immune cells responsible, the reserchers found that specific antigen-presenting cells called dendritic cells were the ones that primarily induced Th17 responses: depletion of vaginal dendritic cells, they saw, decreased the ability of vaginal tissue to promote production of IL-17 in T helper cells, suggesting reduced differentiation into Th17 cells.

This ability of vaginal dendritic cells to induce predominantly Th17 responses was not seen in antigen-presenting cells from spleen, lung, and intestine, suggesting that the hormonal conditioning is unique to the genital mucosa.

Given the increased Th17 responses associated with E2 treatment seen in various experiments, the researchers tested whether IL-17--the immune mediator produced by Th17 cells--played a role in anti-viral immunity against HSV-2. Using "knock-out" mice that lacked IL-17, they found that indeed, IL-17 appears to enhance the anti-viral response by Th1 cells in the vaginal mucosa.

Their study, the researchers summarize, "describes a mechanism by which E2 enhances anti-viral protection following vaccination in the genital HSV-2 mouse model". They add, "to the best of our knowledge, this is the first study demonstrating that E2 can directly regulate T-cell mediated adaptive anti-viral immunity in the female genital tract by modulating DC functions".
In your coverage please use this URL to provide access to the freely available article in PLOS Pathogens:

Please contact if you would like more information.

Funding: This work was supported by Operating Grant to CK: Canadian Institutes of Health Research; Applied HIV Research Chair award to CK: The Ontario HIV Treatment Network (#A); Scholarship award to VCA & KR: Ontario Graduate Scholarship program The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation: Anipindi VC, Bagri P, Roth K, Dizzell SE, Nguyen PV, Shaler CR, et al. (2016) Estradiol Enhances CD4+ T-Cell Anti-Viral Immunity by Priming Vaginal DCs to Induce Th17 Responses via an IL-1-Dependent Pathway. PLoS Pathog 12(5): e1005589. doi:10.1371/journal.ppat.1005589


Related Immune Response Articles:

Researchers decode the immune response to Ebola vaccine
The vaccine rVSV-EBOV is currently used in the fight against Ebola virus.
Immune response depends on mathematics of narrow escapes
The way immune cells pick friends from foes can be described by a classic maths puzzle known as the 'narrow escape problem'.
Signature of an ineffective immune response to cancer revealed
Our immune system is programmed to destroy cancer cells. Sometimes it has trouble slowing disease progression because it doesn't act quickly or strongly enough.
Putting the break on our immune system's response
Researchers have discovered how a tiny molecule known as miR-132 acts as a 'handbrake' on our immune system -- helping us fight infection.
Having stressed out ancestors improves immune response to stress
Having ancestors who were frequently exposed to stressors can improve one's own immune response to stressors, according to Penn State researchers.
Researchers discovered new immune response regulators
The research groups of Academy Professor Riitta Lahesmaa and Research Director Laura Elo from Turku Centre for Biotechnology have discovered new proteins that regulate T cells in the human immune system.
Blueprint for plant immune response found
Washington State University researchers have discovered the way plants respond to disease-causing organisms, and how they protect themselves, leading the way to potential breakthroughs in breeding resistance to diseases or pests.
Immune response mechanism described for fate determination of T cells
In a paper published in the journal Science, University of Alabama at Birmingham researchers and colleagues at four other United States institutions have detailed a mechanism that sets the stage for the fate decision that gives rise to two major subsets of effector cells: T follicular helper cells and non-T follicular helper cells, known as Tfh and non-Tfh cells.
Retinoic acid may improve immune response against melanoma
University of Colorado Cancer Center clinical trial results describe a promising strategy to remove one of melanoma's most powerful defenses: By adding retinoic acid to standard-of-care treatment, researchers were able to turn off myeloid-derived suppressor cells (MDSCs) that turn off the immune system, leading to more immune system activity directed at melanoma.
Enzyme lays the foundations for allergic immune response
While in search of the causes of allergies and asthma, a chance discovery has yielded new clues: researchers led by Dr Marcus Peters have ascertained that the enzyme guanylate cyclase in cells lays the foundations for the type of immune response.
More Immune Response News and Immune Response Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at