Host Protein Induced by the Intestinal Microbiota Signals Neutrophils

A new study investigated whether the effects of the microbiota on immunity could be mediated by Saa (Serum amyloid A). This host protein, which is produced by the intestine and liver in response to the microbiota, has been poorly understood in terms of how it functions in living organisms.

Using normal and mutant zebrafish, researchers from the Duke University School of Medicine, showed that Saa promotes the recruitment of neutrophils to sites of injury, yet restricts the clearance of pathogenic bacterial infection. Analysis of isolated neutrophils revealed that Saa reduces the bactericidal activity of these cells and their expression of pro-inflammatory genes. These effects depend on microbiota colonization, suggesting that the protein mediates the microbiota’s effects on host immunity. Collectively, these data establish that Saa induced by the microbiota in the intestine signals to neutrophils, tuning the extent to which they may be activated by other microbes or respond to injury. Because antibiotic treatment results in reduced intestinal Saa in mice, the researchers suggest that antibiotic treatment could be associated with Saa-mediated aberrations in neutrophil function. They speculate that secondary infections that can occur following antibiotic use could be due in part to concomitant alterations in the production of this protein.

“Our study demonstrates that a host protein made in the intestine following exposure to the microbiota affects innate immune cell populations, both in the gut and other tissues. Microbially responsive secretion of host factors from the intestine can therefore serve as a molecular rheostat which controls the development and function of the host innate immune system,” reported the researchers.

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