Guerra, J. | bioRxiv Science

bioRxiv2020

Detection of hypermucoviscous Klebsiella pneumoniae sequence type 86 capsular type K2 in South America as an unexpected cause of a fatal outbreak in captivity marmosets

After the sudden death of eleven captives marmosets in a rehabilitation center of wildlife in Sao Paulo, Brazil, histological and microbiological study was conducted. Liver, spleen, intestine, central nervous system, lung, thymus, stomach, testicle tissues were analyzed by light microscopy and microbial cultures were conducted. Environmental cultures were also performed. Prophylactic antimicrobial therapy, restricted access to marmosets cages with dedicated staff, and additional sanitization of animals fruits were implemented. Histological findings were compatible with hyperacute septicemia, and microbiological cultures and molecular tests identified the etiologic agent as hypermucoviscous sequence type 86 capsular type K2 K. pneumoniae for the first time in South America. Implementation of prompt containment measures led to successful control of this outbreak. Detection of a hypervirulent and zoonotic pathogen, such as hypermucoviscous K. pneumoniae ST86 K2, in an unexpected and human interface reservoir underscores its potential threat in public health settings.

microbiology↗

bioRxiv2019

Heme induces innate immunity memory

Trained immunity defines long-lasting adaptive responses of innate immunity, mediated by transcriptional and epigenetic modifications of myeloid cells. Here, we report that labile heme, an alarmin released extracellularily upon tissue damage and hemolysis, induces trained immunity in human and murine primary cells and in mice. Heme-trainning in monocytes is associated with epigenetic and transcriptional profiles that overlap to some extent with those seen in {beta}-glucan-training, the prototype agonist of trained immunity. In sharp contrast to {beta}-glucan training however, heme-training relied on activation of the Syk/JNK-pathway. Heme training in mice was associated with long-lasting expansion of myeloid-biased progenitor cells as well as with altered chromatin accessibility in hematopoietic stem and progenitor cells. Finally, heme-induced training was protective against bacterial sepsis in mice. In conclusion, we reveal that heme, a bona fide alarmin, induces innate immune memory regulating host response to infection.

immunology↗