title: Commensal bacteria and MAMPs are necessary for stress-induced increases in IL-1β and IL-18 but not IL-6, IL-10 or MCP-1.
abstract: Regular interactions between commensal bacteria and the enteric mucosal immune environment are necessary for normal immunity. Alterations of the commensal bacterial communities or mucosal barrier can disrupt immune function. Chronic stress interferes with bacterial community structure (specifically, α-diversity) and the integrity of the intestinal barrier. These interferences can contribute to chronic stress-induced increases in systemic IL-6 and TNF-α. Chronic stress, however, produces many physiological changes that could indirectly influence immune activity. In addition to IL-6 and TNF-α, exposure to acute stressors upregulates a plethora of inflammatory proteins, each having unique synthesis and release mechanisms. We therefore tested the hypothesis that acute stress-induced inflammatory protein responses are dependent on the commensal bacteria, and more specifically, lipopolysaccharide (LPS) shed from Gram-negative intestinal commensal bacteria. We present evidence that both reducing commensal bacteria using antibiotics and neutralizing LPS using endotoxin inhibitor (EI) attenuates increases in some (inflammasome dependent, IL-1 and IL-18), but not all (inflammasome independent, IL-6, IL-10, and MCP-1) inflammatory proteins in the blood of male F344 rats exposed to an acute tail shock stressor. Acute stress did not impact α- or β- diversity measured using 16S rRNA diversity analyses, but selectively reduced the relative abundance of Prevotella. These findings indicate that commensal bacteria contribute to acute stress-induced inflammatory protein responses, and support the presence of LPS-mediated signaling in stress-evoked cytokine and chemokine production. The selectivity of the commensal bacteria in stress-evoked IL-1β and IL-18 responses may implicate the inflammasome in this response.
authors.affiliation: Department of Integrative Physiology and the Center for Neuroscience, University of Colorado at Boulder, Boulder, Colorado, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Maslanik
authors.forename: Kate
authors.initials: K
authors.lastname: Tannura
authors.forename: Lucas
authors.initials: L
authors.lastname: Mahaffey
authors.forename: Alice Brianne
authors.initials: AB
authors.lastname: Loughridge
authors.forename: Lida
authors.initials: L
authors.lastname: Beninson
authors.forename: Lida
authors.initials: L
authors.lastname: Benninson
authors.forename: Luke
authors.initials: L
authors.lastname: Ursell
authors.forename: Benjamin N
authors.initials: BN
authors.lastname: Greenwood
authors.forename: Rob
authors.initials: R
authors.lastname: Knight
authors.forename: Monika
authors.initials: M
authors.lastname: Fleshner
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000097:blood; D004597:Electroshock; D016753:Interleukin-10 / Q000097:blood; D020382:Interleukin-18 / Q000097:blood*; D053583:Interleukin-1beta / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018932:Chemokine CCL2; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016753:Interleukin-10