Bacterial clearance in a murine model of lipopolysaccharide tolerance: influence of the site on infection

RODRIGUEZ RODRIGUES, N.; MARTIRE GRECO, D.; LANDONI, V.I.; CHIARELLA, P.; SCHIERLOH, P.; REARTE, B.; ISTURIZ, M.A.; FERNANDEZ, G.C.

Los Cocos, Córdoba

Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología; 2013

SAI

Repeated inoculation of bacterial lipopolysaccharide (LPS) leads to a state of immune hypo-response and immunosuppression, known as tolerance to LPS. This state is similar to the observed in late stages of sepsis. These individuals have increased susceptibility to pulmonary opportunistic infections, sometimes life-threatening. Our aim was to study the response to an infection in the LPS tolerance model, and the relevance of the site of infection in the bacterial clearance. Tolerance was induced by daily i.v. injections of increasing doses of LPS (5-100 μg/day/mouse, Tol) for 7 days. Then the animals were challenged nasally or i.p. with intestinal bacteria (5x106 CFU) and the number of remaining bacteria in the lung or peritoneum was evaluated at 4h and 14h post-infection on McConkey agar plates. We also evaluated the number of neutrophils (PMN) and the levels of TNF-α post-infection. In the lung we observed a decreased bacterial clearance in Tol both at 4 and at 14h post-infection. In contrast, when mice were challenged i.p. with bacteria, the clearance was higher in Tol mice (CFU/ml. Lung 4h: C=25700±8175, Tol=54000±6079, p