Why isn’t a laboratory mouse more like a human? There are several answers, beyond the differences in size and physiology between mice and humans, such as microbiome and immunological experience. Emory researchers led by Mandy Ford and Craig Coopersmith recently published a couple papers that aim to take those factors into account.
The goal is to make mouse immune systems and microbiomes more complex and more like those in humans, so the mice they can better model the deadly derangement of sepsis. So far, sepsis research in mice has been a poor predictor of clinical success. This aligns with work at the National Institutes of Health on “wildling” mice, which have microbes more like wild mice. (Lab Land likes noticing a trend that Emory researchers are part of.)
One Emory paper, in FASEB Journal, shows that mortality in a mouse model of sepsis varies according to the commercial facility where the mice came from. When the mice were allowed to live together and exchange microbes, mortality numbers evened out.
Another, published in JCI Insight, looks at mice that have more memory T cells than naïve mice, since adult humans have a high proportion of memory T cells in their immune systems. Other scientists have shown that sepsis leads to a wipeout of memory T cells, and probably vulnerability in defending against infection. Read more
Interest in bacteria and other creatures living on and inside us keeps climbing. On August 15 and 16, scientists from a wide array of disciplines will gather for the Emory Microbiome Research Center inaugural symposium.
On the first day, Lab Land is looking forward to hearing from several of the speakers, touching on topics stretching from insects/agricultural pathogens to neurodegenerative disease. The second day is a hands on workshop organized by instructor Anna Knight on sorting through microbiome data. The symposium will be at WHSCAB (Woodruff Health Sciences Center Auditorium). Registration before August 2 is encouraged!
Many of the projects that we highlighted four years ago, when Emory held its first microbiome symposium, have continued and gathered momentum. Guest keynotes are from Rodney Newberry from WUSTL and Gary Wu from Penn.
I was struck by one part of Mirko Paiardini’s paper that was published this week in Journal of Clinical Investigation. It describes aÂ treatment aimed at repairing immune function in SIV-infected monkeys, with an eye toward helping people with HIV one day.Â One of the goals of their IL-21 treatment is to restoreÂ intestinal Th17 cells, which are depleted by viral infection.Â In this context, IL-21’s effect is anti-inflammatory.
However, Th17 cells are also involved in autoimmune disease. A recent Cell Metabolism paper from endocrinologist Roberto Pacifici and colleagues examinesÂ Th17 cells, with the goal of treating bone loss coming from an overactive parathyroid. In that situation, too many Th17 cells are bad and they need to be beaten back. Fortunately, bothÂ an inexpensive blood pressure medication and a drugÂ under development for psoriasisÂ seem to do just that.
Note for microbiome fans: connections between Th17 cells and intestinalÂ microbes (segmented filamentous bacteria) are strengthening. It gets complicated because gut microbiota, together with Th17 cells, mayÂ influenceÂ metabolic disease and Th17-like cells are also in the skin — location matters.