Relationship Between Group 3 Innate Lymphoid Cells and Th17 in Human Nasopharynx-Associated Lymphoid Tissue and the Association With Pneumococcal Carriage.

BACKGROUND

Nasopharyngeal carriage of Streptococcus pneumoniae (Sp) in children is common and considered a prerequisite of invasive disease. Group 3 innate lymphoid cells (ILC3) are considered critical in mucosal homeostasis. It is not known if ILC3 play a role in Sp carriage and how ILC3 interact with Sp in the nasopharynx.

METHODS

We characterized ILC3 in the nasopharynx-associated lymphoid tissue of children and adults and examined the relationship of ILC3 with Th17 cells and Sp carriage. We also analyzed the effects of Sp and Staphylococcus aureus on ILC3.

RESULTS

We show that the frequencies of natural cytotoxicity receptor (NCR)+ ILC3 and IL-22-producing ILC3 in the adenotonsillar cells of children were markedly higher than in adults. By contrast, the frequency of Th17 was considerably lower in children than adults. Interestingly, the frequency of NCR+ILC3 in children who were Sp carriage+ve was higher than that of children who were Sp carriage-ve. Furthermore, stimulation of adenotonsillar cells with Sp culture supernatant induced a prominent ILC3 proliferative response and an increase in ILC3 number and level of HLA-DR expression, which correlated with a modest Th17 response. On the contrary, stimulation by S aureus culture supernatant reduced the ILC3 number and was accompanied by a strong Th17 response.

CONCLUSIONS

The abundance of NCR+ILC3 in the nasopharynx of children is positively associated with Sp carriage. The positive relationship between ILC3 and Sp may suggest an important role of ILC3 in the nasopharyngeal carriage of Sp, and further investigation is warranted. Understanding local interactions between ILC3 and ILC3-promoting Sp or ILC3-repressing S aureus may lead to novel therapeutics against nasopharyngeal carriage and disease.