Microbial metabolite protects against infection

Posted by: | October 6, 2023 | Comments


Intestinal dysbiosis is associated with an increased susceptibility to disseminated bacterial infections and sepsis. Kupffer cells, the resident macrophages of the liver that reside within the hepatic vasculature, protect the organ from pathogens and are the first liver cells to come into contact with the blood that is delivered directly to this organ from the gut through the portal vein. McDonald et al. found that mice that were reared germ-free (GF) or treated with antibiotics and then injected with fluorescently labeled Staphylococcus aureus captured less of the pathogen in the liver and exhibited greater bacterial dissemination to the lungs and mortality compared to normally colonized or gnotobiotic mice. Although GF mice had normal numbers of Kupffer cells, the cells were smaller, captured fewer bacteria, and were less efficient at killing bacteria than were Kupffer cells in normally colonized or gnotobiotic mice. The uptake of pathogens by Kupffer cells depended on the bacterial metabolite d-lactate, which was highly abundant in the gut and portal vein blood of normally colonized and gnotobiotic mice but scarce in the systemic circulation and in GF mice. Supplementing GF mice with d-lactate or colonizing them with gut commensals that produce d-lactate restored the abundance of d-lactate in portal vein blood and rescued Kupffer cell size and pathogen capture.

Read more at: Science Signaling

Annalisa M. VanHook, et al. Science Signaling. DOI: 10.1126/scisignal.abe9388. 29 September 2023.

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