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Immune Architecture Altered After Gut Infection in Mouse Study

Discussion in 'Other Health News and Research' started by Bob, Oct 8, 2015.

  1. Bob

    Bob

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    This may be of interest to some of you. It relates to the interaction between gut and immune system, including the issue of chronic gut inflammation.

    Article:
    Infections May Set the Stage for Chronic Inflammatory Diseases
    Immune Architecture Altered After Gut Infection in Mouse Study
    http://www.niaid.nih.gov/topics/immuneSystem/Pages/BelkaidCellFeature.aspx

    Research Paper:
    Microbiota-Dependent Sequelae of Acute Infection Compromise Tissue-Specific Immunity
    http://www.cell.com/cell/abstract/S...m/retrieve/pii/S0092867415010442?showall=true
     
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  2. Simon

    Simon

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    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:
    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.
     
    Last edited: Oct 12, 2015
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  3. Simon

    Simon

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    And here's the paper abstract:
     
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  4. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    [QUOTE="Simon, post: 650239, member: 6724"]

    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.[/QUOTE]

    We have known that short term gut infection can lead to long term gut dysfunction for at least a century - it used to be called tropical sprue. But that was not associated with ME symptoms. You can get a mouse model to do almost anything if you try hard enough so I am not sure this tells us anything very new. I would prefer to see data gathered on real people with ME or related illnesses to be honest.
     
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