Azithromycin Alters Macrophage Phenotype and Pulmonary Compartmentalization during Lung Infection with Pseudomonas

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

Macrolides for the treatment of chronic bacterial prostatitis: An effective application of their unique pharmacokinetic and pharmacodynamic profile (Review)

“…2) (54). Similar changes may be observed in monocytes cultured in vitro and in mice infected with P. aeruginosa (55).…”

Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

“…AZM prevents the progression of lung inflammation in Acinetobacter baumannii-infected mice, without having an antimicrobial effect (71), and alters the macrophage phenotype and pulmonary compartmentalization during P. aeruginosa lung infection (72). Moreover, CLR displays efficacy against an intubation model of induced pneumonia caused by a CLR-resistant NTHI strain in mice, with reductions of bacterial loads and inflammation in CLRtreated animals (45).…”

Neuroprotective Properties of a Macrolide Antibiotic in a Mouse Model of Middle Cerebral Artery Occlusion: Characterization of the Immunomodulatory Effects and Validation of the Efficacy of Intravenous Administration

“…In fact, preservation of alternatively activated M2 microglia/macrophages promotes neuronal survival and functional recovery under ischemic/hypoxic conditions. [8][9][10][86][87][88] The mechanism by which azithromycin shifts macrophages from the classically activated (M1) to the alternatively activated (M2) phenotype has not been completely elucidated [89][90][91] ; however, AP-1 activation and impairment of lysosomal functions may be probably involved. 92,93 These immunomodulatory properties contribute to the clinical efficacy of azithromycin in respiratory diseases, 25 whereas their relevance in neurodegenerative conditions has only been partially explored.…”