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Effect of Laparotomy on Clearance and Cytokine Induction in Staphylococcus aureus–infected Lungs

¹ The Veterans Administration Ann Arbor Healthcare System, Ann Arbor, Michigan; and ² Division of Pulmonary and Critical Care, Department of Internal Medicine, and ³ Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan

Correspondence and requests for reprints should be addressed to Michal Olszewski, D.V.M., Ph.D., Research Service (506/11R), VA Ann Arbor Healthcare System, 2215 Fuller Road, Ann Arbor, MI 48105-2303. E-mail: olszewsm{at}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 10⁸ 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-R suggest suboptimal activation of leukocytes in the lungs of infected LAP animals. Infected LAP mice had decreased expression of interferon (IFN)- 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- 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- induction in the infected lungs of LAP animals is a likely mechanism contributing to the observed phenotype.

Key Words: Staphylococcus aureus • lung • cytokines • innate immunity • macrophages

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Little is known about the natural mechanism of host defenses against the major opportunistic pathogen Staphylococcus aureus. What This Study Adds to the Field Sterile laparotomy produces temporary deactivation of innate immune responses to pulmonary S. aureus infection. Lack of early IFN- induction is a likely mechanism for these findings.