Research tells us that the “good” bacteria that inhabit our intestines help to regulate our metabolism. A new study in fruit flies shows one of the ways in which these commensal microbes keep us metabolically fit.
The findings, published today in Cell Metabolism, suggest that innate immune pathways, our first line of defense against bacterial infection, have a side job that’s equally important.
The intestine’s digestive cells use an innate immune pathway to respond to harmful bacteria by producing antimicrobial peptides. But other intestinal cells, enteroendocrine cells, use the same pathway, known as IMD, to respond to “good” bacteria — by fine-tuning body metabolism to diet and intestinal conditions.
“What’s most interesting to me is that some innate immune pathways aren’t just for innate immunity,” says Paula Watnick, MD, PhD, of the Division of Infectious Diseases at Boston Children’s Hospital. “Innate immune pathways are also listening to the ‘good’ bacteria – and responding metabolically.” …
Once they detect an invader, inflammasomes send out signals that trigger infected cells to die using an inflammatory death pathway called pyroptosis. They also call for backup from the adaptive immune system, in the form of inflammation. (Image: Wu laboratory/Liman Zhang)
If you follow cancer biology, then you’ve probably heard of ubiquitin before. Ubiquitin tags a cell’s damaged or used proteins and guides them to a cellular machine called the proteasome, which breaks them down and recycles their amino acids. Proteasome-blocking drugs like Velcade® that go after that recycling pathway in cancer cells have been very successful at treating two blood cancers—multiple myeloma and mantle cell lymphoma—and may hold promise for other cancers as well.
Less well known, however, is the fact that ubiquitin helps normal, healthy cells raise an alarm when viruses attack. Ubiquitin works with a protein called RIG-I, part of a complex signaling pathway that detects viral RNA and triggers an innate antiviral immune response.
“Why obesity predisposes a person to asthma has been a real puzzle,” says Dale Umetsu, MD, PhD, who recently researched the problem with Hye Young Kim, PhD, and other colleagues in the Division of Allergy and Immunology at Boston Children’s Hospital. “Our goal was to find the connection between these two problems, which occur in both children and adults, and to explore possible new treatments.”
The team’s research indicates that obesity alters the innate immune system—the body’s first responder to infection—in several ways, resulting in lung inflammation. Published earlier this month in Nature Medicine, their work also suggests a completely new, “druggable” approach to treating patients with obesity-associated asthma, for whom standard asthma drugs often work poorly. …
Our immune system has immense powers of observation. It needs to in order to fend off the millions of bacteria, viruses, fungi, you name it, that we get exposed to every day.
I’m not talking about antibodies and T cells—parts of the immune system’s adaptive arm, which is fine-tuned to recognize a specific virus or bacterium. Rather, I’m talking about pattern recognition proteins—biological sensors capable of recognizing features and structures that only bacteria or viruses have. These make up the immune system’s innate arm, which essentially primes the body to attack anything that looks remotely like it doesn’t belong.
For instance, our cells carry sensors that can detect double-stranded RNA (dsRNA), which certain kinds of viruses use to encode their genome—like the rotavirus, which causes severe diarrhea in infants and small children. Our genome, by contrast, is encoded in DNA, and the RNA we make is single-stranded; if there’s dsRNA present, it means there’s a virus around.