Cutibacterium acnes, a crusty Cheeto-shaped bug that lives on human skin, loves the oily pocket around hair follicles. No face is as oily as that of teenagers, flooded with hormones that grow hair, deepen voices and accelerate the production of sebum, a secretion that makes skin a moist, protective barrier.
Too little sebum means dry, scaly skin, like patches of eczema. Too much sebum means acne, the skin disease caused by C. acnes. Bumps, pimples and blackheads grow on most teenagers and, increasingly, on the faces of young adults, even in their 20s and 30s. And, in people with extra-oily skin, the body’s natural defenses seem unable to get rid of the bacteria.
A new study in Sciences Immunology gives clues as to why more than 45 million people suffer from acne, a disease that has been proven psychologically and socially devastating For the young. Directed by Robert ModlinProfessor Klein of Dermatology at UCLA, a team of researchers discovered overzealous and underperforming immune cells.
Macrophages are one of the first responders of our immune system. They rush to the site of a problem and are instructed to clean, remove dead cells, and get rid of pathogens and other unwanted treats. When it comes to acne-prone skin, macrophages are called upon to absorb extra oils – lipids – and kill bacteria that cause clogged pores and inflammation (that big red bump on a friend’s forehead). But something about the oil, a component of sebum called squalene, turns what should be a garbage truck into a reservoir for the growth of C. acnes bacteria. The Modlin lab studied the skin from the backs of six people — nearly 33,000 cells from day-old acne lesions and 29,000 cells from non-lesional skin — and simulated acne lesions in petri dishes to find a potential answer.
After analyzing the genetic sequencing, Tran Do, an MD-Ph.D. student and main author of the article, had the idea of putting squalene directly in the box with the regular macrophages. What emerged were those mysterious “foamy” macrophages, called Trem2 macrophages, which Do later found mentioned in articles about other chronic fat-related diseases.
Trem2 macrophages clustered around fatty hair follicles, acting like nightmare guests. They got to work and stuffed themselves by gulping down as much oil as they could, but were “overly optimistic about the fat buffet,” Modlin said. Instead of defeating C. acnes, macrophages were stripped of their infection-fighting powers (although it’s still unclear how). One tactic: Squalene in the belly of a frothy macrophage finds oxygen radicals – molecules that can kill acne bacteria – and incorporates them into its oily stew, neutralizing the threat, leaving acne flourish.
“This acne bacteria is specialized to live there,” said Modlin, who is also a professor of microbiology, immunology and molecular genetics at UCLA. “It uses the lipids in that environment to grow, and it also worked with the host to avoid being killed.”
The research, published Friday, helps explain on a more granular level why benzoyl peroxide, a popular but irritating first-line treatment for acne, works. What Trem2 macrophages cannot accomplish, benzoyl peroxide can: overcome squalene’s oxygen radical-absorbing trick to kill acne bacteria. Knowing more about a particular pathway that leads to acne can open the door to other treatments or understanding why certain treatments, like the powerful drug Accutane, are so effective at curing acne, said Alvin Codadermatologist at the Scripps Clinic in La Jolla, California.
“You can have 10 different drugs with 10 different targets to treat one disease,” Coda said, because skin diseases are so complex, with inflammation being driven by multiple complex processes. The American Academy of Dermatology acne guidelines suggest that the best approach is to reduce sebum production, open pores and reduce inflammation. While research has affirmed since the late 19th century that C. acnes is involved in the formation of acne lesions, scientists are still studying exactly how and why acne occurs. Most agree that it is a multifactorial disease and that no one cause is to blame.
Understanding how lipids suppress the body’s immune response also has bigger implications, Modlin said. He found his way to research on leprosy acne (Hansen’s disease), his main area of study, as the two diseases share a genetically similar bacterial infection. In some forms of leprosy, foamy macrophages can harbor hundreds of bacteria in each cell – an extreme version of what occurs in acne patients. “Your pimples go away in two or three days, so you end up defeating the bacteria,” he said. In severe leprosy, “the bacteria wins”.
But many other conditions, including certain forms of non-alcoholic fatty liver disease, obesity, Alzheimer’s disease, certain cancers, foamy cell tuberculosis and atherosclerosis, could be caused by foamy macrophages Trem2 “probably identical “.
In Alzheimer’s disease, there is an increase in Trem2-expressing macrophages – microglia – which scoop up lipids in the brain. In nonalcoholic steatohepatitis (fatty liver disease), researchers found more than Trem2 macrophages in the liver. These macrophages are also increased in many cancers, Harmeet Malhi, a consultant in the Mayo Clinic’s division of gastroenterology and hepatology, told STAT in an email. “Another interesting observation is that the age distribution of the three conditions does not overlap significantly, suggesting that these lipid-responsive macrophages may be involved in disease throughout life,” she says.
What scientists glean from inside pimples could eventually lead to the development of more targeted acne treatments and also help advance understanding of other chronic lipid-related conditions.