Pretreatment with the Gram-positive bacterial cell wall molecule peptidoglycan improves bacterial clearance and decreases inflammation and mortality in mice challenged with Pseudomonas aeruginosa.

Murphey ED, Sherwood ER
Microbes Infect. 2008 10 (12-13): 1244-50

PMID: 18678270 · PMCID: PMC2603308 · DOI:10.1016/j.micinf.2008.07.021

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.

MeSH Terms (13)

Animals Cell Wall Gram-Positive Bacteria Immunity, Innate Inflammation Male Mice Mice, Inbred C3H Mice, Inbred C57BL Peptidoglycan Pseudomonas aeruginosa Pseudomonas Infections Staphylococcus aureus

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