3 years ago

OTITIS MEDIA AND NASOPHARYNGEAL COLONIZATION IN CCL3(-/-) MICE.

Wasserman SI, Deniffel D, Kurabi A, Hung J, Nuyen B, Ryan AF, Suzukawa K, Pak K
Introduction. We previously found CC chemokine ligand 3 (CCL3) to be a potent effector of inflammation during otitis media (OM): exogenous CCL3 rescues the OM phenotype of tumor necrosis factor-deficient mice, and function of macrophages deficient in several innate immune molecules. To further delineate the role of CCL3 in OM, we evaluated middle ear (ME) responses of ccl3-/- mice to nontypeable Haemophilus influenzae (NTHi).Materials and Methods. CCL chemokine gene expression was evaluated in wildtype (WT) mice during the complete course of acute OM. OM was induced in ccl3-/- and WT mice, and infection and inflammation monitored for 21 days. Phagocytosis and killing of NTHi by macrophages was evaluated by in vitro assay. Nasopharyngeal bacterial load was assessed in naive animals of both strains.Results. Many CCL genes increased expression during acute OM, with CCL3 the most upregulated at 600x baseline. Ccl3-/- deletion compromised ME bacterial clearance and prolonged mucosal hyperplasia. ME recruitment of leukocytes was delayed, but persisted far longer than in WTs. These events were linked to a decrease in macrophage capacity for NTHi phagocytosis and increased nasopharyngeal bacterial load in ccl3-/- mice. The generalized impairment in inflammatory cell recruitment was associated with compensatory changes in the expression profiles of CCL2, CCL7 and CCL12.Conclusions. CCL3 plays a significant role in clearance of infection and resolution of inflammation, and contributes to mucosal host defense of the nasopharyngeal niche, a reservoir for ME and upper respiratory infection. Therapies based on CCL3 could prove useful in treating or preventing persistent disease.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28847849

DOI: PubMed:28847849

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