NETs: protection from pathogens or men

Alright a colleague of mine gave a talk a few weeks ago in an extremely informal format (yes booze was involved). Anyway these talks tend to be over-the-top excellent, not because of the content, but because they tend to be thought provoking. These are talks that have not been sterilized by the rigorous standards usually associated with polished talks. They often represent ideas without much data to back them up, pilot studies, etc. For this scientist, these are a blast!

Anyway, the talk was only peripherally associated with this post, in fact there were a couple of specific pictures shown and statements made that, in conjunction with some facts I am aware of, led me to the following thoughts. (BTW bitches, this is how science works at its best!)

First, you need to know about neutrophils. In short, neutrophils are one of the asskicking cells of the immune system (this is the system that has allowed you to live long enough to read this). When you are infected (and you are currrently infected with a bunch of things), your cells recruit neutrophils and other immunologic cells to the sites of infection to basically go ape-shit on the infectious particle's ass. Neutrophils are the kamikaze fighters of your immune system. While I am in fact being metaphorical here, in many ways the kamikaze analogy holds up well. When combatting infectious agents, such as bacteria or fungi, neutrophils act like suicide bombers secreting enzymes that are destructive or make destructive toxic chemicals that kill the infecting particle and the neutrophil (for the record the primary component of pus, the gunk you squeeze out of your forehead when combatting zits) is basically the carcasses of dead neutrophils that gave up their lives to the cause).

Now the self-sacrifice of neutrophils has long been known. However, it has recently been demonstrated that these dead neutrophils have an additional function. The DNA from these dead neutrophils is released into the environment and makes up a meshwork of DNA and enzymes that act essentially as nets to trap infectious microbes and kill them with the associated enzymes. These structures are aptly termed NETs (neutrophil extracellular traps) and are reviewed here (subscription required).

Now I realize all of this neutrophil biology is really cool, but what is the point?

Neutrophils, and other cells, can be extruded across epithelial cell layers into the lumenal environment of various tissues. In the vaginal cavity, neutrophils are extruded across the vaginal squamous epithelia where they can interact and kill resident bacteria. Now the vaginal cavity is home normally to bacteria, namely the Lactobaccili. However, these normal, commensal, bacteria do not cause neutrophils to do this. This property is left to non-resident microbes, in other words pathogens. When pathogenic bacteria and fungi colonize the vaginal track, neutrophils extrude through the epithelial cell layer, enter the vaginal cavity and attack the microbes, dying in the process, building NETs and continuing to kill microbes. The link between the microbe and the neutrophil is actually the epithelial cells. Epithelial cells sense the presence of pathogenic microbes and send signals to the neutrophils, essentially telling them to "CHARGE!" (More on this story in another post)

Now what's interesting is that sex also causes the same effect. Neutrophil extrusion. The question is why. My short answer would have been epithelial damage that occurs during the physical process of sex. Even the best sex causes some damage to the vaginal mucosa. However, that short answer would have been wrong, or at least incomplete. It turns out that if you simply add seminal fluid to vaginal epithelial cells, the epithelial cells respond to recruit the neutrophils. So vaginal epithelial cells respond to seminal fluid in about the same way that they respond to Neisseria gonorrhoeae bacterium. Which brings us to the painful fact, that for all you men out there, your significant others bodies still view you as a bad thing.

Now this linkage of neutrophil extrusion with sex makes a lot of sense. When you engage in sex, you are always taking a risk. No matter how much your partner swears fidelity, there's always a chance they are lying. So potentially your mate may be bringing something to the table you weren't planning on. Further, the female is at greatest risk here because of the physical trauma associated with the act and the fact most of the of the relevant secretions are within her body. So having a potent immunological cell dive into the frenzy to deal with these potential problems is a good, albeit untested AFAIK, idea.

Now I got to thinking, which is not necessarily a good thing, that while an immune response to the seminal fluid is a good idea to protect the female could there be other factors in play here? For example, maybe there is a selective advantage to males by having promoting an immunologic response in the female reproductive track. For example, once sex is over, the female may seek out other mates, if you are the first male, then maybe the elicited immunologic response kills off competing sperm. This would certainly increase your chance of being the lucky genome donor. Maybe females are most likely to breed with the "optimal" mate first and then, in social species like primates, breed with less optimal mates for political reasons (food sharing for instance). This would increase the chance that your genes are mixed with those the genes of the optimal mate and not the slack jawed yokel monkey who just happened to find black gold, texas tea in them there hills.

Again AFAIK these ideas have not been tested, but I think they are interesting and potentially thought provoking. This is a reason I love science, its fun to play arm chair theoretician.