How does the host actually degrade LPS? Macrophages phagocytose bacteria and make use of the autopathic machinery to ‘digest’ the pathogen, suggesting that autophagy likely also degrade the bacteria-derived LPS. In fact, I found an article (only the abstract) demonstrating that LPS accumulate “in phagocytic vacuoles of hepatic Kupffer cells, splenic macrophages, and leukocytes.” (see:http://www.jimmunol.org/content/123/5/2133).
This all suggests that LPS in likely degraded by autophagy, but I cannot find a single article demonstrating this explicitly.
Do anyone know if autophagy does, in fact, degrade LPS? A citable reference would be awesome.
Hi Gustav van Niekerk,
Hope the article enclosed herein will give you some insights.
Regards
Selvam.
Many thanks for the interesting article Selvam! This article, however, only report on the observation that rapamycin-induced autophagy help mice cope with 10 days of EtOH feeding followed by a challenge with LPS. The study does not address the question as to whether autophagy is involved in degrades LPS. (In fact, the authors focus on ROS production in formulating a hypothesis as to how upregulating autophagy is protective -no mention of autophagy-mediated LPS degradation)
There are numerous similar studies showing a beneficial effect of upregulated autophagy in context of sepsis or a simulation thereof (i.e. LPS challenge). What I’m interested in an article explicitly describing if/how autophagy is involved in the degradation/metabolism of LPS.
Hi Zuoyang Qin, many thanks for the detailed response!
As I understand, the procedure you explained would give an indication of autophagic activity (autopathic flux).
But what we need is to verify that autophagic apparatus is indeed deployed in the degradation of LPS. Of course, it would be nice to show that an increase in autophagic activity correlate with a lower inflammatory response following LPS challenge: this would suggest that autophagy may be responsible for processing the LPS into less noxious substrate.
However, this would only be a correlation, not a definitive proof that it is because of lysosomal degradation of LPS (i.e. the induction of autophagy may exert an anti-inflammatory effect that is distinct from the degradation of LPS).
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