Azithromycin alters macrophage phenotype and pulmonary compartmentalization during lung infection with Pseudomonas

David J. Feola, Beth A. Garvy, Theodore Cory, Susan E. Birket, Heather Hoy, Don Hayes, Brian S. Murphy

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Infection with mucoid strains of Pseudomonas aeruginosa in chronic inflammatory diseases of the airway is difficult to eradicate and can cause excessive inflammation. The roles of alternatively activated and regulatory subsets of macrophages in this pathophysiological process are not well characterized. We previously demonstrated that azithromycin induces an alternatively activated macrophage-like phenotype in vitro. In the present study, we tested whether azithromycin affects the macrophage activation status and migration in the lungs of P. aeruginosa-infected mice. C57BL/6 mice received daily doses of oral azithromycin and were infected intratracheally with a mucoid strain of P. aeruginosa. The properties of macrophage activation, immune cell infiltration, and markers of pulmonary inflammation in the lung interstitial and alveolar compartments were evaluated postinfection. Markers of alternative macrophage activation were induced by azithromycin treatment, including the surface expression of the mannose receptor, the upregulation of arginase 1, and a decrease in the production of proinflammatory cytokines. Additionally, azithromycin increased the number of CD11b+ monocytes and CD4+ T cells that infiltrated the alveolar compartment. A predominant subset of CD11b+ cells was Gr-1 positive (Gr-1 +), indicative of a subset of cells that has been shown to be immunoregulatory. These differences corresponded to decreases in neutrophil influx into the lung parenchyma and alteration of the characteristics of peribronchiolar inflammation without any change in the clearance of the organism. These results suggest that the immunomodulatory effects of azithromycin are associated with the induction of alternative and regulatory macrophage activation characteristics and alteration of cellular compartmentalization during infection.

Original languageEnglish (US)
Pages (from-to)2437-2447
Number of pages11
JournalAntimicrobial Agents and Chemotherapy
Volume54
Issue number6
DOIs
StatePublished - Jun 1 2010

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Pseudomonas Infections
Azithromycin
Alveolar Macrophages
Macrophage Activation
Phenotype
Lung
Pseudomonas aeruginosa
Macrophages
Inflammation
Arginase
Infection
Inbred C57BL Mouse
Monocytes
Pneumonia
Neutrophils
Chronic Disease
Up-Regulation
Cytokines
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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Azithromycin alters macrophage phenotype and pulmonary compartmentalization during lung infection with Pseudomonas. / Feola, David J.; Garvy, Beth A.; Cory, Theodore; Birket, Susan E.; Hoy, Heather; Hayes, Don; Murphy, Brian S.

In: Antimicrobial Agents and Chemotherapy, Vol. 54, No. 6, 01.06.2010, p. 2437-2447.

Research output: Contribution to journalArticle

Feola, David J. ; Garvy, Beth A. ; Cory, Theodore ; Birket, Susan E. ; Hoy, Heather ; Hayes, Don ; Murphy, Brian S. / Azithromycin alters macrophage phenotype and pulmonary compartmentalization during lung infection with Pseudomonas. In: Antimicrobial Agents and Chemotherapy. 2010 ; Vol. 54, No. 6. pp. 2437-2447.
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