Lora Hooper is a professor in the Department of Immunology at the University of Texas Southwestern Medical Center (Dallas), and an investigator at the Howard Hughes Medical Institute. Her lab studies immune mechanisms that prevent bacteria from crossing intestinal barriers and entering host tissues.
Hooper sat down to talk with GMFH editors at the Keystone Symposium earlier this month.
How do bacteria try to invade the intestinal epithelium?
There’s a multi-step process. First, there’s attachment to the epithelial cell and [in my Keystone talk I covered] the fact that that triggers expression of antimicrobial proteins such as REG3 gamma [regenerating islet-derived protein 3 gamma], which is one that we work on, but there are others.
The epithelial cell desperately wants to get rid of the bacteria so those proteins are secreted from the surface of the epithelial cell, and the idea is to keep bacteria from attaching because that restricts the amount of invasion that occurs.
When they do invade, which does sometimes happen, especially if there’s a pathogen – it’s not very well understood what the response of the epithelial cell is to invasion. One thing we have shown is that one defense mechanism that’s very important is autophagy… we’ve shown that when bacteria invade epithelial cells you get activation of autophagic pathways. Basically, the cell senses – and we don’t know how this happens – it senses that there’s a bacterium in it. Of course, that’s a bad thing, so in a really fascinating set of molecular processes, it surrounds it with a membrane, ‘cordons it off’ from everything else and then it shuttles it to a lysosome. Basically, the bacteria gets chewed up, dies, and the cell gets rid of it.
Do you think diet can impact these processes?
Autophagy’s a very interesting process to think about in terms of how diet might impact that, because autophagy traditionally has been studied in the context of what happens during starvation. So in addition to being an important way in which a cell defends itself against invading bacteria and viruses, autophagy can also get activated when a cell is starving… it starts eating itself and using its own organelles for nutrients. So autophagy is involved in that pathway.
An interesting question we haven’t addressed yet, that I would like to address in the lab is: if you deprive yourself of glucose, or you’re starving – let’s say it’s a short-term proposition – will you activate autophagy that then might help protect you against bacteria? So what happens: are epithelial cells more protected against bacterial invasion when we’re nutrient deprived or starving? There might be some crosstalk there.
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