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

Abstract

The generation of tissue-resident memory T cells (T RM ) is an essential aspect of immunity at mucosal surfaces, and it has been suggested that preferential generation of T RM 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 T RM 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 T RM. 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 + T RM in the nasal mucosa. These results demonstrate a critical and sufficient role of T RM 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.Mucosal Immunology (2020) 13:172-182; https://doi.

Tissue resident memory T cells in the respiratory tract

“…In bacterial infection models of Streptococcus pneumoniae 108 , 109 , Bordetella pertussis 110 , Klebsiella pneumoniae 76 , and Mycobacterium tuberculosis 111 , 112 respiratory tract CD4 + Trm have been shown to contribute to bacterial clearance, typically via the production of the pro-inflammatory cytokines IL-17 and IFNγ. An interesting report by Shenoy et al 113 provides insight into how mouse CD4 + Trm improves bacterial clearance from the lung.…”

Expansion of tissue-resident CD8+ T cells and CD4+ Th17 cells in the nasal mucosa following mRNA COVID-19 vaccination

“…It has been hypothesized that Trm may be the most effective form of T cell response against SARS-CoV-2 infection 31 , capable of preventing viral dissemination beyond the URT, where more virus-induced damage can occur 32 . Data from mice have suggested that parenteral vaccination induces nasal Th17 Trm that protect against bacterial colonization 33,34 . However, our study is the first, to our knowledge, to suggest nasal T cells may be induced by parenteral vaccination against COVID-19.…”

Tissue-resident memory T cells in tumor immunity and immunotherapy

“…Compared with their protective role in infectious diseases ( Wu et al, 2018 ; Wilk and Mills, 2018 ; Muruganandah et al, 2018 ; O’Hara et al, 2020 ), the importance and significance of T RM in tumor immunity are not adequately characterized. Nevertheless, recent studies in cancer-bearing mouse models have indicated a pivotal role of T RM in antitumor immunity in several tumor types ( Nizard et al, 2017 ; Milner et al, 2017 ; Malik et al, 2017 ; Enamorado et al, 2017 ).…”