The Lipopolysaccharide Core of Brucella abortus Acts as a Shield Against Innate Immunity Recognition

Innate immunity recognizes bacterial molecules bearing pathogen-associated molecular patterns to launch inflammatory responses leading to the activation of adaptive immunity. However, the lipopolysaccharide (LPS) of the gram-negative bacterium Brucella lacks a marked pathogen-associated molecular pattern, and it has been postulated that this delays the development of immunity, creating a gap that is critical for the bacterium to reach the intracellular replicative niche. We found that a B. abortus mutant in the wadC gene displayed a disrupted LPS core while keeping both the LPS O-polysaccharide and lipid A. In mice, the wadC mutant induced proinflammatory responses and was attenuated. In addition, it was sensitive to killing by non-immune serum and bactericidal peptides and did not multiply in dendritic cells being targeted to lysosomal compartments. In contrast to wild type B. abortus, the wadC mutant induced dendritic cell maturation and secretion of pro-inflammatory cytokines. All these properties were reproduced by the wadC mutant purified LPS in a TLR4-dependent manner. Moreover, the core-mutated LPS displayed an increased binding to MD-2, the TLR4 co-receptor leading to subsequent increase in intracellular signaling. Here we show that Brucella escapes recognition in early stages of infection by expressing a shield against recognition by innate immunity in its LPS core and identify a novel virulence mechanism in intracellular pathogenic gram-negative bacteria. These results also encourage for an improvement in the generation of novel bacterial vaccines

Symphyseal fixation in open book injuries cannot fully compensate anterior SI joint injury-A biomechanical study in a two-leg alternating load model.

In open book injuries type Tile B1.1 or B1.2 also classified as APC II (anteroposterior compression), it remains controversial, if a fixation of the anterior ring provides sufficient stability or a fixation of the posterior ring should be included. Therefore the relative motion at the sacroiliac joint was quantified in a two-leg alternating load biomechanical pelvis model in the intact, the injured and the restored pelvis.Fresh-frozen intact (I) pelvises (n = 6) were subjected to a non-destructive cyclic test under sinosuidal axial two-leg alternating load with progressively increasing amplitude. Afterwards an open book injury (J) including the anterior ligament complex of the left sacroiliac joint, the sacrospinal and sacrotuberal ligaments (Tile B1.1) was created and the specimens were retested. Finally, the symphysis was stabilized with a modular fixation system (1-, 2- or 4-rod configuration) (R) and specimens were cyclically retested. Relative motion at the sacroiliac joint was captured at both sacroiliac joints by motion tracking system at two load levels of 170 N and 340 N during all tests.Relative sacroiliac joint movements at both load levels were significantly higher in the J-state compared to the I-state, excluding superoinferior translational movement. With exception of the anteroposterior translational movement at 340N, the relative sacroiliac joint movements after each of the three reconstructions (1-, 2-, 4-rod fixation) were significantly smaller compared to the J-state and did not differ significantly to the I-state, but stayed above the values of the latter. Relative movements did not differ significantly in a direct comparison between the 1-rod, 2-rod and 4-rod fixations.Symphyseal locked plating significantly reduces relative movement of the sacroiliac joint in open book injuries type Tile B1.1 or B1.2 (APC II) but cannot fully restore the situation of the intact sacroiliac joint