Macrolides Promote CCL2-Mediated Macrophage Recruitment and Clearance of Nasopharyngeal Pneumococcal Colonization in Mice

The Journal of Infectious Diseases
Naoki IwanagaShigeru Kohno

Abstract

Streptococcus pneumoniae (pneumococcus) colonizes mucosal surfaces of the upper respiratory tract (URT), resulting in invasive disease. Macrolides are known for their immunomodulatory effects. We investigated the potency of macrolides to reduce pneumococcal colonization by activating host innate immunity. The kinetics of colonization, cellular response, and inflammatory cytokine levels in the URT were assessed after nasal inoculation of pneumococci. EM900 (a novel 12-membered nonantibiotic macrolide with an immunomodulatory effect) was orally administered throughout the experiment. Survival was evaluated for 10 days. Macrolide-mediated CCL2 production from peritoneal macrophages was determined by enzyme-linked immuosorbent assay. The cell-signaling pathway was analyzed by means of Western blotting and gene silencing assays. Streptococcus pneumoniae was significantly reduced from EM900-treated mice 14 days after pneumococcal inoculation. Macrophage recruitment and Ccl2 messenger RNA expression were promoted. CCL2 production from peritoneal macrophages was significantly induced by macrolides and was dependent on NF-κB phosphorylation through the myeloid differentiation primary-response gene 88- or TIR domain-containing adapter-in...Continue Reading

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Citations

Mar 28, 2018·Antimicrobial Agents and Chemotherapy·Bruno CorsiniJose Yuste
Dec 11, 2019·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Hironori SadamatsuNaoko Sueoka-Aragane
Apr 3, 2019·Antimicrobial Agents and Chemotherapy·Shigeki NakamuraYoshitsugu Miyazaki

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