Toll-Like Receptors 2 and 4 Modulate Pulmonary Inflammation and Host Factors Mediated by Outer Membrane Vesicles Derived from Acinetobacter baumannii

Abstract

Pneumonia due to Gram-negative bacteria is associated with high mortality. <i>Acinetobacter baumannii</i> is a Gram-negative bacterium that is associated with hospital-acquired and ventilator-associated pneumonia. Bacteria have been described to release outer membrane vesicles (OMVs) that are capable of mediating systemic inflammation. The mechanism by which <i>A. baumannii</i> OMVs mediate inflammation is not fully defined. We sought to investigate the roles that Toll-like receptors (TLRs) play in <i>A. baumannii</i> OMV-mediated pulmonary inflammation. We isolated OMVs from <i>A. baumannii</i> cultures and intranasally introduced the OMVs into mice. Intranasal introduction of <i>A. baumannii</i> OMVs mediated pulmonary inflammation, which is associated with neutrophil recruitment and weight loss. In addition, <i>A. baumannii</i> OMVs increased the release of several chemokines and cytokines in the mouse lungs. The proinflammatory responses were partially inhibited in TLR2- and TLR4-deficient mice compared to those of wild-type mice. This study highlights the important roles of TLRs in <i>A. baumannii</i> OMV-induced pulmonary inflammation <i>in vivo</i>.