Editors' ChoiceMICROBIOTA

Neutrophils Block Bacterial Flood in Gut Infection

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Science Translational Medicine  02 Oct 2013:
Vol. 5, Issue 205, pp. 205ec162
DOI: 10.1126/scitranslmed.3007664

Rising floodwaters often worsen damage to homes and communities during storms, making flood control a priority in natural disasters. Like floodwaters, commensal bacteria in the family Enterobacteriaceae swell within the intestine during infections and magnify disease severity, making it necessary for infected hosts to contain both commensals and the inciting pathogen to restore health.

Molloy and colleagues studied the host response to commensal Enterobacteriaceae overgrowth during acute Toxoplasma gondii infection in mice to understand how hosts limit their exposure to these potentially pathogenic commensal bacteria during infection. They found that host cells surrounded commensal bacteria in intraluminal cast structures that physically separated bacteria from the mucosa and minimized bacterial translocation during T. gondii infection. Moreover, intraluminal levels of Enterobacteriaceae were restored to baseline relatively quickly after an initial period of expansion, which suggests that excess Enterobacteriaceae bacteria were cleared as part of this process. Neutrophils were the primary host cell type involved in forming the intraluminal casts, and neutrophil depletion prevented cast formation and increased bacterial translocation and mortality. Mechanistically, neutrophil recruitment and intraluminal cast formation were linked to the detection of N-formyl peptides from Enterobacteriaceae via a high-affinity receptor, and mice lacking this receptor also had reduced intraluminal cast formation and worse outcomes. Thus, neutrophils sense the metabolic byproducts of Enterobacteriaceae as part of the commensal microbiota and respond by sequestering them within intraluminal casts for clearance from the intestine.

This study reveals a process by which hosts limit epithelial contact and systemic invasion by potentially pathogenic commensal bacteria during acute mucosal infection. Additional studies are needed to verify the formation and significance of intraluminal casts in humans and other inflammatory intestinal disorders and the effects of neutropenia on commensal bacterial containment in clinical patients.

M. J. Molloy et al., Intraluminal containment of commensal outgrowth in the gut during infection-induced dysbiosis. Cell Host Microbe 14, 318–328 (2013). [Abstract]

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