Septic mice are susceptible to pulmonary aspergillosis.
Clinical data underscores the fact that subsequent high mortality rates occur in patients who survive acute septic episodes. Herein, we described a clinically relevant model of experimental sepsis that we believe will allow further investigation of the manner in which the pulmonary innate immune response is modulated after sepsis. C57BL/6 mice were subjected to cecal ligation and puncture (CLP) model, whereby the cecum was partially ligated and punctured nine times with a 21-gauge needle. This procedure was associated with 100% mortality at 3 days after surgery. In contrast, when mice subjected to CLP were treated with antibiotic beginning at 8 hours after surgery, and every 12 hours thereafter until 3 days, approximately 60% of the mice survived. Interestingly, CLP survivors quickly succumbed (100% mortality) to pulmonary infection when intratracheally challenged, at day 3 after CLP, with viable Aspergillus fumigatus conidia. No mortality was observed in conidia-challenged sham-operated mice. The defective innate immune response against A. fumigatus in CLP mice could not be explained by a failure of neutrophils to infiltrate the lungs. Instead, gene array analysis revealed that several components of the innate immune response, including the nuclear factor-kappaB signaling pathway, were down-regulated. Thus, we describe a system of sepsis-induced innate immune failure in the lungs of C57BL/6 mice.
Benjamim
Claudia F
CF
Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109-0602, USA.
Hogaboam
Cory M
CM
Lukacs
Nicholas W
NW
Kunkel
Steven L
SL
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001228:Aspergillosis / Q000209:etiology* / Q000235:genetics; D001232:Aspergillus fumigatus; D001424:Bacterial Infections / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004198:Disease Susceptibility; D015536:Down-Regulation; D005260:Female; D007962:Leukocytes / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008172:Lung Diseases, Fungal / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes; D016328:NF-kappa B / Q000235:genetics; D020556:Neutrophil Infiltration; D010529:Peritoneal Cavity; D010538:Peritonitis / Q000382:microbiology*; D012720:Severity of Illness Index; D016019:Survival Analysis
D000900:Anti-Bacterial Agents; D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B