A dynamic relationship between mucosal Th17 and Treg populations in nasopharynx evolves with age and associates with the clearance of pneumococcal carriage in humans

Ayman Mubarak, Muhammad S Ahmed, Nav Upile, Casey Vaughan, Carol Xie, Ravi Sharma, Priya Acar, Maxwell S McCormick, James C Paton, Tim Mitchell, Nigel Cunliffe, Qibo Zhang

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26 Citations (Scopus)
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Abstract

OBJECTIVES: Pneumococcal carriage is common in young children that may account for the high incidence of disease in this age group. Host factors determining the clearance of carriage in humans remain unclear. We aimed to study the relationships between Th17 and Foxp3+Treg in nasopharynx-associated lymphoid tissue (NALT) and carriage in children and adults.

METHODS: Frequencies of Th17 and Treg in NALT were analyzed by flow-cytometry in association with age and pneumococcal carriage status. Cytokine resonses following pneumococcal stimulation was analyzed by cytometric beads array.

RESULTS: The frequencies of Th17 and Treg in NALT were inversely correlated (R=-0.60). Whilest Treg frequency decreased with age (R=-0.63), both Th17 and the Th17/Treg ratio increased with age (R=0.62 & 0.64 respectively). Also, the Th17/Treg ratio was higher in carriage-negative than in carriage-positive children (p<0.01). Pneumococcal stimulation of tonsillar cells increased both Th17 and Treg numbers, but the Th17/Treg ratio and pattern of cytokine responses differed between carriage-ve and carriage+ve children. The former showed markedly higher Th17/Treg and IL17A/IL10 ratios than that in the latter (p<0.01). Pneumococcal stimulation also induces Th17, although the capacity of this Th17 differentiation from naïve T cells of young children was low, but increased with age.

CONCLUSIONS: We demonstrated a dynamic relationship between Th17 and Treg in human nasopharynx that evolves with age. The balance between Th17 and Treg in NALT appears a major host factor closely associated with the clearance of S.pneumoniae from the nasopharynx.

Original languageEnglish
JournalClinical Microbiology and Infection
Early online date30 May 2016
DOIs
Publication statusE-pub ahead of print - 30 May 2016

Keywords

  • Children and adults
  • cytokine response
  • Mucosal Th17
  • Nasopharynx-associated lymphoid tissue (NALT)
  • pneumococcal carriage
  • Streptococcus pneumoniae
  • T regulatory cells (Treg)

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