title: Pretreatment with the Gram-positive bacterial cell wall molecule peptidoglycan improves bacterial clearance and decreases inflammation and mortality in mice challenged with Pseudomonas aeruginosa.
abstract: The objective of this study was to determine if inflammatory tolerance and enhancement of innate immune function could be induced by the Gram-positive cell wall component peptidoglycan (PGN). Male mice (C57BL6/J or C3H/HeJ, 8-12 weeks of age) were given intraperitoneal injections of 1mg PGN on 2 consecutive days. The mice were then challenged with lipopolysaccharide (LPS) or live Pseudomonas aeruginosa (1 x 10(8) colony-forming units) 2 days after the second pretreatment. Mice pretreated with PGN had diminished plasma concentrations of TNFalpha and IFNgamma and elevated concentrations of IL-10 in response to a subsequent LPS or Pseudomonas challenge when compared to untreated controls. Bacterial clearance was improved in mice pretreated with PGN, and mortality in response to a subsequent Pseudomonas challenge was significantly attenuated. PGN pretreatment of LPS-unresponsive mice (C3H/HeJ) verified that the effect of PGN pretreatment was not due to any LPS contamination. We have previously demonstrated that PGN pretreatment induced resistance to a Gram-positive bacterial challenge. The present study extends those results by showing that exposure to the Gram-positive bacterial cell wall component peptidoglycan also induces cross-tolerance to LPS and non-specifically enhances innate immune function in that PGN-pretreated mice had increased resistance to Gram-negative bacterial challenge.
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, 301 University Ave, Galveston, TX 77555-0591, USA. edmurphe@utmb.edu
authors.forename: E D
authors.initials: ED
authors.lastname: Murphey
authors.forename: E R
authors.initials: ER
authors.lastname: Sherwood
mesh_terms: D000818:Animals; D002473:Cell Wall / Q000737:chemistry; D006094:Gram-Positive Bacteria / Q000737:chemistry* / Q000276:immunology; D007113:Immunity, Innate; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010457:Peptidoglycan / Q000008:administration & dosage* / Q000276:immunology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000401:mortality*; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification / Q000472:pathogenicity*; D013211:Staphylococcus aureus / Q000737:chemistry / Q000276:immunology
chemical_list: D010457:Peptidoglycan