Format

Send to

Choose Destination
PLoS Pathog. 2015 Jun 24;11(6):e1005004. doi: 10.1371/journal.ppat.1005004. eCollection 2015 Jun.

Clearance of Pneumococcal Colonization in Infants Is Delayed through Altered Macrophage Trafficking.

Author information

1
Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
2
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.
3
Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

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.

PMID:
26107875
PMCID:
PMC4479461
DOI:
10.1371/journal.ppat.1005004
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center