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Female reproductive tract plays defense

The immune system of the female reproductive tract has a big job to fulfill," says Dartmouth physiologist Patricia Pioli, Ph.D. That "big job" includes fending off a multitude of invading microorganisms but also knowing which foreign cells not to attack, such as sperm and the cells of a developing fetus. So how does the system do that?

Attack: This is one of the questions that Pioli and her colleagues are trying to answer. They study the innate immune response of the female reproductive tract. Innate immunity is the body's initial response to an invading pathogen. This front-line defense attacks pathogens nonspecifically, without factoring in previous exposure, as acquired immunity does. Recent studies have shown that tolllike receptors (TLRs) are important in initiating innate immune responses in several types of human cells. TLRs are molecules found on cell surfaces that act as "watchdogs" for the cells. They recognize invaders and send signals to the inside of the cell, culminating in the production and recruitment of immune cells to combat the infection. Pioli and several colleagues recently published a paper suggesting that TLRs mediate the innate immune response in the human female reproductive tract. They have

Patricia Pioli is probing the immune system.

been able to show the presence of several types of TLRs throughout the tract.

The team's latest paper, in the journal Infection and Immunity, focuses on two kinds of toll-like receptors‹TLR2 and TLR4. Different tissues of the reproductive tract are exposed to different types and amounts of pathogens and must mount a response accordingly. For example, the tissues in the lower part of the tract are exposed to a large number and a wide array of bacteria and viruses, whereas far fewer pathogens make it to the upper part of the tract. TLR2 and TLR4 are able to recognize different types of pathogens, and this paper shows that the two receptors are present in differing

levels in the different tissues of the tract.

Levels: An especially interesting finding was that low levels of both TLRs were found in the lowest part of the reproductive tract, where the most pathogens are present. This may seem counterintuitive, but, as Pioli explains, "it's actually not surprising, because there is a whole host of organisms that are encountered in that part of the tract and you really wouldn't want to mount an inflammatory response to every single bacteria," since chronic inflammation of the tract would have many harmful effects.

What's next for Pioli? "What I'm looking at right now is the influence of estrogen and progesterone on toll-like receptor expression," she says. The levels of these hormones fluctuate during the menstrual cycle and throughout pregnancy. Recognizing how they regulate TLR levels in the tissues of the reproductive tract may yield insight into how the innate immune system functions at different times during the menstrual cycle and pregnancy‹to defend against an array of pathogens and also to provide an environment conducive Patricia Pioli is probing the immune system. to reproduction.

Kristen Garner

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