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Updated: Aug 30, 2026
Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
Septic mice are susceptible to pulmonary aspergillosis
Claudia F Benjamim1, Cory M Hogaboam, Nicholas W Lukacs
1Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109-0602, USA.
Abstract:
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.
Insights
Sepsis survivors exhibit high mortality due to subsequent infections. This study details a sepsis model in mice showing impaired lung immunity, leading to fatal pulmonary infections and down-regulated immune pathways.
Area of Science:
- Immunology
- Infectious Disease
- Critical Care Medicine
Background:
- High mortality rates persist in patients surviving acute sepsis.
- Pulmonary complications significantly contribute to sepsis-related deaths.
- Understanding post-sepsis immune dysregulation is crucial for improving patient outcomes.
Purpose of the Study:
- To establish a clinically relevant mouse model for investigating sepsis-induced pulmonary immune modulation.
- To explore the mechanisms underlying impaired lung immunity following sepsis.
- To identify specific immune pathways affected by sepsis.
Main Methods:
- Cecal ligation and puncture (CLP) procedure in C57BL/6 mice to induce sepsis.
- Antibiotic treatment initiated post-CLP to improve survival rates.
- Intratracheal challenge with Aspergillus fumigatus conidia in CLP survivors.
- Gene array analysis to assess pulmonary immune gene expression.
Main Results:
- The CLP model demonstrated high mortality, with antibiotic treatment improving survival to ~60%.
- CLP survivors exhibited 100% mortality upon subsequent pulmonary challenge with Aspergillus fumigatus.
- Gene array analysis revealed down-regulation of innate immune components, including the nuclear factor-kappaB pathway, in CLP mice lungs.
Conclusions:
- A mouse model of sepsis-induced pulmonary immune failure was successfully established.
- Sepsis compromises the lung's innate immune response, increasing susceptibility to opportunistic infections.
- Down-regulation of key signaling pathways like NF-κB contributes to this immune deficiency.
