The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi

Discussion in 'Lyme Disease and Co-Infections' started by Vitalic, Apr 29, 2016.

  1. Vitalic

    Vitalic Senior Member

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    J Leukoc Biol. 2016 Apr 21. pii: jlb.4A0715-331R. [Epub ahead of print]
    Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi.
    Buffen K1, Oosting M1, Li Y2, Kanneganti TD3, Netea MG1, Joosten LA4.

    Abstract
    We have previously demonstrated that inhibition of autophagy increased the Borrelia burgdorferi induced innate cytokine production in vitro, but little is known regarding the effect of autophagy on in vivo models of Borrelia infection. Here, we showed that ATG7-deficient mice that were intra-articular injected with Borrelia spirochetes displayed increased joint swelling, cell influx, and enhanced interleukin-1β and interleukin-6 production by inflamed synovial tissue. Because both interleukin-1β and interleukin-6 are linked to the development of adaptive immune responses, we examine the function of autophagy on Borrelia induced adaptive immunity. Human peripheral blood mononuclear cells treated with autophagy inhibitors showed an increase in interleukin-17, interleukin-22, and interferon-γ production in response to exposure to Borrelia burgdorferi.Increased IL-17 production was dependent on IL-1β release but, interestingly, not on interleukin-23 production. In addition, cytokine quantitative trait loci in ATG9B modulate the Borrelia induced interleukin-17 production. Because high levels of IL-17 have been found in patients with confirmed, severe, chronic borreliosis, we propose that the modulation of autophagy may be a potential target for anti-inflammatory therapy in patients with persistent Lyme disease.

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    I found this particularly interesting because my IL-17 is notably elevated. I would be interested to know if anyone else has observed that -- KDM suggested it indicated autoimmune activation. Since I've been through IV treatment and the value did not go down I wonder if it actually indicates a maladaptive immune response to low levels of Borrelia keeping the patient under a persistent inflammatory condition.
     
    Last edited: May 1, 2016
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  2. Hip

    Hip Senior Member

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    If you search for: Lyme | Borrelia IL-17 | Th17 you see that the Th17 immune response and IL-17 arises during Borrelia infections (the cytokine IL-17 is secreted by Th17 immune cells).


    The question then arises as to whether inhibiting or boosting the Th17 immune response is beneficial in Lyme disease.

    By inhibiting Th17, this might lower inflammation and thereby improve symptoms. Also, high Th17 is linked to autoimmunity, so lowering Th17 may have beneficial effects on quelling autoimmune responses. But it might conceivably also allow Borrelia to proliferate more.

    By boosting Th17, this might increase the fight against Borrelia; or it may just ramp up inflammation without have much antibacterial benefit against Borrelia, and may worsen autoimmunity.

    It says here that:
    Although it says here that it's not clear where the IL-17 is coming from in Lyme:


    There are a number of Th17 inhibitors, such as those listed in this post.

    The Th17 immune response is also involved in fighting Candida and Staphylococcus.
     
    Last edited: Apr 30, 2016
  3. Vitalic

    Vitalic Senior Member

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    Thanks for the summary. I updated the post with an actual link to the study by the way. This study was talking about autophagy and that if it is diminished it can increase IL-17 production, they propose modulation of autophagy which I presume means trying to increase it with the aim of reducing inflammation. But then as you point out the key question is whether you still have an active/persistent infection and whether dampening the immune response is going to be beneficial in the overall picture. This is a difficult question. But I did not realise the potential significance of this marker, on a personal level I was siding towards believing (largely due to the complete failure of treatment) that I perhaps never had Lyme and that I had received some false positives, and it is somewhat annoying this evidence keeps cropping up challenging my internal narrative :nervous:

    Looks like there are some agents that increase autophagy: http://www.invivogen.com/autophagy-inducers
     
  4. Hip

    Hip Senior Member

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    Interesting link.

    The usual major trigger for autophagy is fasting. I would think most of the touted health benefits of fasting come from the fact fasting ramps up autophagy. In autophagy, cells clear out the "gunk" inside them.

    I read that for some pathogenic infections, autophagy helps fight the infection; but for other pathogens, autophagy can almost be beneficial for the pathogen. Coxsackievirus B is on pathogen that benefits from autophagy (having said that, I have active an coxsackievirus B infection, and was fine after a 2 month juice fast on 700 kilocalories daily).
     

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