The Toll-Like Receptor 4 Agonist Monophosphoryl Lipid A Augments Innate Host Resistance to Systemic Bacterial Infection

• DOI: 10.1128/iai.00022-11
• Publication Date: 2011-06-07T04:40:50Z
• Authors: Christopher D. Ro...; Tushar K. Varma; Jason B. Hobbs; Aimee Reyes; Brandon Driver; Edward R. Sherwood
• Keywords: Proinflammatory cytokine

ABSTRACT Monophosphoryl lipid A (MPLA) is a Toll-like receptor 4 (TLR4) agonist that currently used as vaccine adjuvant in humans. In this study, we evaluated the effect of MPLA treatment on innate immune response to systemic bacterial infections mice. Mice treated with after burn injury showed improved survival and less local dissemination bacteria model Pseudomonas aeruginosa wound infection. Prophylactic significantly enhanced clearance at site infection reduced despite causing attenuation proinflammatory cytokine production during acute intra-abdominal caused by cecal ligation puncture. Administration 1 h CLP also but did not alter production. increased numbers granulocytes, double-positive myeloid cells, macrophages sites percentage total cells mediating phagocytosis bacteria. Depletion Ly6G + neutrophils, macrophages, eliminated ability improve clearance. The immunomodulatory effects were absent TLR4-deficient conclusion, these studies show augments enhancing mediated, part, effective phagocytic functions TLR4 dependent.