Tolerance to lipopolysaccharide promotes an enhanced neutrophil extracellular traps formation leading to a more efficient bacterial clearance in mice.

VERÓNICA I. LANDONI; PAULA CHIARELLA; DAIANA MARTIRE-GRECO; SCHIERLOH PABLO LUIS; VAN-ROOIJEN N; REARTE B; PALERMO MS; MARTÍN A. ISTURIZ; GABRIELA C. FERNÁNDEZ

CLINICAL AND EXPERIMENTAL IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2012 vol. 168 p. 153 - 163

0009-9104

Tolerance to lipopolysaccharide (LPS) constitutes a stress adaptation, in which a primary contact with LPS results in a minimal response when a second exposure with the same stimulus occurs. However, during the tolerant state, active important defense mechanisms are mounted. Our aim was to assess the contribution of neutrophils (PMN) in the clearance of bacterial infection in a mouse model of tolerance to LPS. After tolerance was developed, we investigated in vivo different mechanisms of bacterial clearance. The elimination of a locally induced polymicrobial challenge was more efficient in tolerant mice both in the presence or absence of local macrophages. This was related to a higher number of PMN migrating to the infectious site, as a result of an increased number of PMN from the marginal pool with higher chemotactic capacity, and not because of differences in their phagocytic activity or reactive species production. In vivo, NETs destruction by nuclease treatment abolished the observed increased clearance in tolerant but not control mice. In line with this finding, in vitro neutrophil extracellular traps (NETs) formation was higher in PMN from tolerant animals. These results indicate that the higher chemotactic response from an increased PMN marginal pool and the NETs enhanced forming capacity are the main mechanisms mediating bacterial clearance in tolerant mice. To sum up, far from being a lack of response, tolerance to LPS causes PMN priming effects which favor distant and local anti-infectious responses.