TY - JOUR
T1 - Combined loss of cRel/p50 subunits of NF-?B leads to impaired innate host response in sepsis
AU - Courtine, Emilie
AU - Cognard, Nicolas
AU - Mazzolini, Julie
AU - Antona, Marion
AU - Pene, Frederic
AU - Fitting, Catherine
AU - Jacques, Sebastian
AU - Rousseau, Christope
AU - Niedergang, Florence
AU - Gerondakis, Steven Demetrious
AU - Chiche, Jean-Daniel
AU - Ouaaz, Fatah
AU - Mira, Jean-Paul
PY - 2012
Y1 - 2012
N2 - NF-?B, which comprises homo- and hetero-dimers of the five members of the Rel family, plays a crucial role in immunity to infection. The cRel and p50 subunits have been implicated in the development and function of the immune cells, but their in vivo importance remains poorly explored in sepsis. We aimed to study the impact of the combined loss of these two subunits on the innate response to infection in a cecal ligation and puncture model of sepsis. We have explored the possible defects in host defense, including pathogen clearance, bacterial phagocytosis and cytokine plasma release. We also performed gene profiling of cRel-/-p50-/- and wild-type LPS-stimulated peritoneal macrophages. Deficiency of cRel and p50 led to enhanced mortality to sepsis that was associated with defective macrophages phagocytosis, decreased bacterial clearance and moderate cytokine response. Transcription profile analysis revealed a common inflammatory response but a significant down-regulated transcription of genes encoding for pathogen recognition receptors and antimicrobial molecules, supporting the in vivo findings in mice. In conclusion, the cRel and p50 subunits of NF-?B play an important combined role in the innate response and are crucial for survival and pathogen clearance in polymicrobial sepsis. ? The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav
AB - NF-?B, which comprises homo- and hetero-dimers of the five members of the Rel family, plays a crucial role in immunity to infection. The cRel and p50 subunits have been implicated in the development and function of the immune cells, but their in vivo importance remains poorly explored in sepsis. We aimed to study the impact of the combined loss of these two subunits on the innate response to infection in a cecal ligation and puncture model of sepsis. We have explored the possible defects in host defense, including pathogen clearance, bacterial phagocytosis and cytokine plasma release. We also performed gene profiling of cRel-/-p50-/- and wild-type LPS-stimulated peritoneal macrophages. Deficiency of cRel and p50 led to enhanced mortality to sepsis that was associated with defective macrophages phagocytosis, decreased bacterial clearance and moderate cytokine response. Transcription profile analysis revealed a common inflammatory response but a significant down-regulated transcription of genes encoding for pathogen recognition receptors and antimicrobial molecules, supporting the in vivo findings in mice. In conclusion, the cRel and p50 subunits of NF-?B play an important combined role in the innate response and are crucial for survival and pathogen clearance in polymicrobial sepsis. ? The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav
UR - http://ini.sagepub.com/content/18/5/753.full.pdf
U2 - 10.1177/1753425912440296
DO - 10.1177/1753425912440296
M3 - Article
SN - 1753-4259
VL - 18
SP - 753
EP - 763
JO - Innate Immunity
JF - Innate Immunity
IS - 5
ER -