INVESTIGADORES
GAMBERALE Romina
artículos
Título:
Bacterial DNA activates human neutrophils by a CpG-independent pathway
Autor/es:
TREVANI ANALIA; CHORNY ALEJO; SALAMONE GABRIELA; VERMEULEN MÓNICA; GAMBERALE ROMINA; SCHETTINI JORGE; RAIDEN SILVINA; GEFFNER JORGE
Revista:
EUROPEAN JOURNAL OF IMMUNOLOGY
Editorial:
WILEY-V C H VERLAG GMBH
Referencias:
Año: 2003 vol. 33 p. 3164 - 3174
ISSN:
0014-2980
Resumen:
Bacterial DNA stimulates macrophages,
monocytes, B lymphocytes, NK cells, and dendritic cells in a
CpG-dependent manner. In this work we demonstrate that bacterial DNA,
but not mammalian DNA, induces human neutrophil activation as assessed
by L-selectin shedding, CD11b upregulation, and stimulation of cellular
shape change, IL-8 secretion, and cell migration. Induction of these
responses is not dependent on the presence of unmethylated CpG motifs,
as neutrophil stimulatory properties were neither modified by
CpG-methylation of bacterial DNA nor reproduced by oligonucleotides
bearing CpG motifs. We found that human neutrophils express Toll-like
receptor (TLR) 9 mRNA. However, as expected for a CpG-independent
mechanism, activation does not involve a TLR9-dependent signaling
pathway; neutrophil stimulation was not prevented by immobilization of
bacterial DNA or by wortmannin or chloroquine, two agents that inhibit
TLR9 signaling. Of note, both single-stranded and double-stranded DNA
were able to induce activation, suggesting that neutrophils might be
activated by bacterial DNA at inflammatory foci even in the absence of
conditions required to induce DNA denaturation. Our findings provide the
first evidence that neutrophils might be alerted to the presence of
invading bacteria through recognition of its DNA via a novel mechanism
not involving CpG motifs.