From initial infection to chronic illness (gut microbiome implicated)
This is a really interesting study, but pretty complex too. It uses a mouse model, infecting mice with a bug that infects humans too, to study long-term consequences for the immune system of infection - in some individuals - after the original infection has been cleared. While the authors focus on inflammatory disorders, particularly gut problems like Crohn's disease, it could conceivably play a role in mecfs, though that is pure speculation on my part.
The basic idea is that sometimes after an infection, infected tissues do not recover to their pre-infection state, leaving an 'immune scar' that causes long-term inflammation/immune dysfunction.This could 'set the stage for chronic disease by impairingthe immune system’s checks and balances' accordig to a paywalled
commentary by Carl Nathan in the same journal
The study appeared in
Cell, one of the very top journals alongside
Nature.
brief video summarising the idea:
Nasty stomach bug affecting humans, mice and others
The researchers used the bacteria
Yersinia pseudotuberculosis which when given orally causes nasty stomach infections in mice, humans and other mammals. It can also cause swollen gut lymph glands in humans, so this isn't a typical infection, though the authors argue the effects are not unique to this particular organism.
Y pseudotuberculosis is a relative of
Yersinia Pestis, which causes the plague(!)
Healthy recovery vs long-term problems
Most mice had cleared the infection after three weeks. Yet 70% had long-term problems and "persistently leaky lymphatic vessels draining the intestine and persistently enlarged, inflamed lymph glands in the mesentery (a broad membrane in the abdomen)". These changes are similar to what's seen in humans, and lasted up to 42 weeks (equivalent to 28 years in humans).
Dendritic cells, which play a key role in presenting antigens to activate other immune cells, accumulated in nearby adipose tissue (fat) instead of lymph nodes, and the tissue also produced inflammatory cytokines.
Reduces ability to mount an appropriate immune response
Mice that recovered from the infection developed an immune responset to a new protein in their food, instead of becoming tolerant to it, a finding linked to dysfuction of T-regulatory cells. On the other hand, they failed to mount a normal immune response to a vaccine.
Role for microbiome
The authors argue that the long-term, harmful immune changes are sustained by products of the gut microbiome, and antibiotics that wipe out the microbiome restore normal immune function.
Leaky gut and chronic infection?
The commentary by Nathan suggests another, or additional interpretation based on the studies finding of "infection of the mesenteric lymph glands by bacteria other than Yersinia, chiefly lactobacilli. Lactobacilli are usually thought of as beneficial—people swallow them as probiotics." He suggests that this opportunistic infection by normally-harmless bacteria could be responsible for maintaing the 'immune scar', but it isn't clear cut. He concludes:
the persistent immune dysfunction observed by da Fonseca et al. may indicate that acute infection by a known pathogen can create a context for an otherwise innocuous microbe to become a chronic pathogen.
Whatever the explanation, the observations of da Fonseca et al. are likely to breathe new life into the search for infectious provocateurs of chronic immune and inflammatory disorders, whether the trigger is a transient infection by a known pathogen or a cryptic, chronic infection by a microbe that is usually nonpathogenic.
This is all a bit over my head, and I'd be very interested to hear the views of
@Jonathan Edwards on this (who I know is sceptical of the relevance of mice models of immune problems to human disease).
Worth taking a look at the
'video abstract' of the paper, which lasts under 5 mins.
