Commensal microflora induce host defense and decrease bacterial translocation in burn mice through toll-like receptor...

Area of Science:

• Immunology
• Gastroenterology
• Trauma Research

Background:

• Major burns compromise gut barrier function, leading to increased bacterial translocation (BT).
• The role of commensal microflora in modulating host defense and BT following burn injury remains to be fully elucidated.

Purpose of the Study:

• To investigate if gut commensal microflora can induce host defense mechanisms and reduce bacterial translocation in a murine burn model.
• To determine the specific role of toll-like receptor 4 (TLR4) in mediating these effects.

Main Methods:

• Commensal microflora depletion using antibiotics in wild-type (WT) mice, followed by lipopolysaccharide (LPS) administration to activate TLR4.
• Assessment of intestinal permeability, inflammatory markers (NF-kappaB, MPO, TNFalpha), TLR4 expression, bacterial killing activity, and BT to mesenteric lymph nodes (MLNs).
• Evaluation of LPS effects in TLR4-mutant (C3H/HeJ) mice and WT mice post-burn.

Main Results:

• Burn injury increased BT in WT mice. Commensal depletion impaired host defense, reducing TLR4 expression and bacterial killing activity.
• Oral LPS administration significantly reduced burn-induced BT by 81% and enhanced immune cell activity and TLR4 expression.
• LPS treatment had no effect on BT or bacterial killing in TLR4-mutant mice, indicating TLR4-dependency.

Conclusions:

• Commensal microflora are crucial for inducing intestinal TLR4 expression and inflammatory cell activity in burn injury.
• Activation of TLR4 by its ligand (LPS) enhances bacterial killing and significantly decreases burn-induced BT.
• The findings confirm that commensal microflora, via TLR4 signaling, bolster host defense and mitigate bacterial translocation in burn-injured mice.