title: Clearance of Pneumococcal Colonization in Infants Is Delayed through Altered Macrophage Trafficking.
abstract: Infections are a common cause of infant mortality worldwide, especially due to Streptococcus pneumoniae. Colonization is the prerequisite to invasive pneumococcal disease, and is particularly frequent and prolonged in children, though the mechanisms underlying this susceptibility are unknown. We find that infant mice exhibit prolonged pneumococcal carriage, and are delayed in recruiting macrophages, the effector cells of clearance, into the nasopharyngeal lumen. This lack of macrophage recruitment is paralleled by a failure to upregulate chemokine (C-C) motif ligand 2 (Ccl2 or Mcp-1), a macrophage chemoattractant that is required in adult mice to promote clearance. Baseline expression of Ccl2 and the related chemokine Ccl7 is higher in the infant compared to the adult upper respiratory tract, and this effect requires the infant microbiota. These results demonstrate that signals governing macrophage recruitment are altered at baseline in infant mice, which prevents the development of appropriate innate cell infiltration in response to pneumococcal colonization, delaying clearance of pneumococcal carriage.
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Siegel
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Department of Ophthalmology, Otorhinolaryngology, and Head and Neck Surgery, Ribeirao Preto School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Edwin
authors.initials: E
authors.lastname: Tamashiro
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weiser
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000502:physiology*; D018932:Chemokine CCL2 / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008810:Mice, Inbred C57BL; D009305:Nasopharynx / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000254:growth & development* / Q000276:immunology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D022242:Pneumococcal Vaccines