Generation of protective pneumococcal-specific nasal resident memory CD4+ T cells via parenteral immunization.

Abstract:

:The generation of tissue-resident memory T cells (TRM) is an essential aspect of immunity at mucosal surfaces, and it has been suggested that preferential generation of TRM is one of the principal advantages of mucosally administered vaccines. We have previously shown that antigen-specific, IL-17-producing CD4+ T cells can provide capsular antibody-independent protection against nasal carriage of Streptococcus pneumoniae; but whether pneumococcus-responsive TRM are localized within the nasal mucosa and are sufficient for protection from carriage has not been determined. Here, we show that intranasal administration of live or killed pneumococci to mice generates pneumococcus-responsive IL-17A-producing CD4+ mucosal TRM. Furthermore, we show that these cells are sufficient to mediate long-lived, neutrophil-dependent protection against subsequent pneumococcal nasal challenge. Unexpectedly, and in contrast with the prevailing paradigm, we found that parenteral administration of killed pneumococci also generates protective IL-17A+CD4+ TRM in the nasal mucosa. These results demonstrate a critical and sufficient role of TRM in prevention of pneumococcal colonization, and further that these cells can be generated by parenteral immunization. Our findings therefore have important implications regarding the generation of immune protection at mucosal surfaces by vaccination.

journal_name

Mucosal Immunol

journal_title

Mucosal immunology

authors

O'Hara JM,Redhu NS,Cheung E,Robertson NG,Patik I,Sayed SE,Thompson CM,Herd M,Lucas KB,Conaway E,Morton CC,Farber DL,Malley R,Horwitz BH

doi

10.1038/s41385-019-0218-5

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

172-182

issue

1

eissn

1933-0219

issn

1935-3456

pii

10.1038/s41385-019-0218-5

journal_volume

13

pub_type

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