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Published on: June 15, 2019
Effect of laparotomy on clearance and cytokine induction in Staphylococcus aureus infected lungs
Michal A Olszewski1, Nicole R Falkowski, Rishi Surana
1The Veterans Administration Ann Arbor Healthcare System, Ann Arbor, Michigan 48105-2303, USA. olszewsm@umich.edu
Rationale:
Staphylococcus aureus is a major pathogen complicating postsurgical care.
Objectives:
To test the effect of sterile laparotomy (LAP) on pulmonary clearance of S. aureus in a murine model.
Methods:
Control and LAP mice were infected intranasally with 10(8) cfu of S. aureus. Microbial clearance, pulmonary leukocyte recruitment, and cytokine profiles were compared between the groups. Antibody neutralization or cytokine gene knockout mice were used to evaluate the role of cytokines.
Measurements And Main Results:
Laparotomy resulted in a 10-fold increase in S. aureus lung colony-forming units on Days 2 and 3 postinfection. Both groups cleared the infection by Day 4. No defect in leukocyte recruitment into the lungs was observed in infected LAP animals; however, an increase in the number of Mac-3-positive cells and a significant decrease of cells with high surface expression of Fc-gammaR suggest suboptimal activation of leukocytes in the lungs of infected LAP animals. Infected LAP mice had decreased expression of interferon (IFN)-gamma and increased expression of mRNA for IL-13 in the lungs on Day 1 postinfection and decreased levels of IL-6, keratinocyte-derived chemokine (KC), and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage at Day 2 postinfection. Neutralization of IFN-gamma mimicked the effect of LAP with impaired clearance on Day 2.
Conclusions:
Sterile LAP induced temporary deactivation of innate immune responses to pulmonary S. aureus challenge. Impaired microbial clearance was accompanied by altered cytokine expression and suboptimal activation of pulmonary leukocytes. Lack of early IFN-gamma induction in the infected lungs of LAP animals is a likely mechanism contributing to the observed phenotype.
Insights
Sterile laparotomy (LAP) temporarily impairs the lung
Area of Science:
- Immunology
- Infectious Diseases
- Surgical Research
Background:
- Staphylococcus aureus is a significant pathogen that complicates postsurgical care.
- Understanding the impact of surgical procedures on host defense mechanisms is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the effect of sterile laparotomy (LAP) on the pulmonary clearance of Staphylococcus aureus.
- To elucidate the underlying immune mechanisms, including leukocyte function and cytokine profiles, affected by LAP during S. aureus infection.
Main Methods:
- Murine model of intranasal Staphylococcus aureus infection.
- Comparison of microbial clearance, pulmonary leukocyte recruitment, and cytokine expression between control and laparotomy groups.
- Utilized antibody neutralization and gene knockout models to assess the role of specific cytokines, particularly interferon-gamma (IFN-γ).
Main Results:
- Laparotomy led to a 10-fold increase in S. aureus lung burden on Days 2 and 3 post-infection, with full clearance by Day 4.
- While leukocyte recruitment was not impaired, LAP animals showed suboptimal leukocyte activation (increased Mac-3, decreased Fc-γR expression).
- LAP mice exhibited decreased IFN-γ and increased IL-13 mRNA in lungs on Day 1, and reduced IL-6, KC, and MIP-2 in bronchoalveolar lavage on Day 2. IFN-γ neutralization mimicked LAP's impaired clearance.
Conclusions:
- Sterile laparotomy induces a transient deactivation of innate immune responses against pulmonary S. aureus.
- Impaired microbial clearance is associated with altered cytokine profiles and suboptimal pulmonary leukocyte activation.
- Reduced early IFN-γ induction in the lungs of LAP animals is a key mechanism contributing to this impaired host defense phenotype.
