INVESTIGADORES
CHIARELLA Paula
artículos
Título:
Tolerance to lipopolysaccharide promotes an enhanced neutrophil extracellular traps formation leading to a more efficient bacterial clearance in mice.
Autor/es:
VERÓNICA I. LANDONI; PAULA CHIARELLA; DAIANA MARTIRE-GRECO; SCHIERLOH PABLO LUIS; VAN-ROOIJEN N; REARTE B; PALERMO MS; MARTÍN A. ISTURIZ; GABRIELA C. FERNÁNDEZ
Revista:
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Lugar: Londres; Año: 2012 p. 153 - 163
ISSN:
0009-9104
Resumen:
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, active important
defence mechanisms are mounted during the tolerant state. Our aim was to
assess the contribution of polymorphonuclear 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, not because of differences in
their phagocytic activity or reactive species production. In vivo, neutrophils
extracellular trap (NET) destruction by nuclease treatment abolished the
observed increased clearance in tolerant but not in control mice. In line with
this finding, in vitro 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 favour distant and local anti-infectious responses.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, not because of differences in
their phagocytic activity or reactive species production. In vivo, neutrophils
extracellular trap (NET) destruction by nuclease treatment abolished the
observed increased clearance in tolerant but not in control mice. In line with
this finding, in vitro 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 favour distant and local anti-infectious responses.In vivo, neutrophils
extracellular trap (NET) destruction by nuclease treatment abolished the
observed increased clearance in tolerant but not in control mice. In line with
this finding, in vitro 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 favour distant and local anti-infectious responses.in vitro 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 favour distant and local anti-infectious responses.