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Tomasz Ahrends and coworkers report that "Enteric pathogens induce tissue tolerance and prevent neuronal loss from subsequent infections". A visual 
inspired by politics with a graphical anstract at the end. https://www.biorxiv.org/content/10.1101/2021.04.09.439221v1
inspired by politics with a graphical anstract at the end. https://www.biorxiv.org/content/10.1101/2021.04.09.439221v1
@MatheisFanny @paulandmull and colleagues previously reported that various (non-neurotropic) enteric pathogens, including a less pathogenic form of Salmonella, lead to acute loss of enteric neurons, in a Caspase 11, NLRP6-dependent manner https://www.cell.com/cell/fulltext/S0092-8674(19)31328-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867419313285%3Fshowall%3Dtrue
Having Brazilians in the lab, Tomasz asked a timely question: "do consecutive infections with unrelated pathogens (so no immunological memory) result in cumulative neuronal loss, so that eventually infected animals show in the gut as few neurons as @jairbolsonaro has in his
"?
"?
We set up several infections models to answer that relevant question, we really hoped that @jairbolsonaro phenotype was not common in other species, right @barronjohn1946?
We infected mice with Y. pseudotuberculosis we got from @BrodskyIgor and found, after animal cleared Yersinia, the resistance to Salmonella (spiB) was the same as (Y.p.)-uninfected mice; however, gut motility was no longer delayed by Salmonella infection.
Conversely, we found that previous infection history with Y.p. prevented Salmonella-induced neuron loss. This was mediated by muscularis macrophages MM (depleted by anti-CSF1R Abs we got from @MiriamMerad) that upregulated arginase-1 in response to adrenergic receptors signaling
An even more impressive disease tolerance phenotype (no change in pathogen load with improved host fitness) was observed with previous helminth (Strongyloids venezuelensis, S.v.) infection, which completed prevented spiB-induced neuronal loss and delayed motility
However, S.v. infection did not induce activation of gut sympathetic neurons, and conversely did not depend on b2AR-expression by muscularis macrophages (MM)
Helminth infection induced IL-4/IL-13-producing eosinophils, which distally induced tissue-protective MM that prevented subsequent spiB-induced neuronal loss... Mice were protected up to 6 months after S.v. (!!) clearance, due to long term effects on Eos bone-marrow precursors
We not only found a mechanism for long-term tissue tolerance induced by pathogens, but we also could not confirm @jairbolsonaro phenotype, suggesting there's hope for 
and other nations dealing with this kind of fascists! Thanks everyone involved in this study!
and other nations dealing with this kind of fascists! Thanks everyone involved in this study!
