Bystander activation of Bordetella pertussis-induced nasal tissue-resident memory CD4 T cells confers heterologous immunity to Klebsiella pneumoniae
Citation:
Lucy M. Curham, Jenny M. Mannion, Clíodhna M. Daly, Mieszko M. Wilk, Lisa Borkner, Stephen J. Lalor, Rachel M. McLoughlin, Kingston H.G. Mills, 'Bystander activation of Bordetella pertussis-induced nasal tissue-resident memory CD4 T cells confers heterologous immunity to Klebsiella pneumoniae', European Journal of Immunology, 2023;0:2250247Download Item:
Abstract:
Tissue-resident memory CD4 T (TRM) cells induced by infection with Bordetella pertussis persist in respiratory tissues and confer long-term protective immunity against reinfection. However, it is not clear how they are maintained in respiratory tissues. Here, we demonstrate that B. pertussis-specific CD4 TRM cells produce IL-17A in response to in vitro stimulation with LPS or heat-killed Klebsiella pneumoniae (HKKP) in the presence of dendritic cells. Furthermore, IL-17A-secreting CD4 TRM cells expand in the lung and nasal tissue of B. pertussis convalescent mice following in vivo administration of LPS or HKKP. Bystander activation of CD4 TRM cells was suppressed by anti-IL-12p40 but not by anti-MHCII antibodies. Furthermore, purified respiratory tissue-resident, but not circulating, CD4 T cells from convalescent mice produced IL-17A following direct stimulation with IL-23 and IL-1β or IL-18. Intranasal immunization of mice with a whole-cell pertussis vaccine induced respiratory CD4 TRM cells that were reactivated following stimulation with K. pneumoniae. Furthermore, the nasal pertussis vaccine conferred protective immunity against B. pertussis but also attenuated infection with K. pneumoniae. Our findings demonstrate that CD4 TRM cells induced by respiratory infection or vaccination can undergo bystander activation and confer heterologous immunity to an unrelated respiratory pathogen.
Sponsor
Grant Number
Science Foundation Ireland
15/SIRG/3426
Author's Homepage:
http://people.tcd.ie/millsk
Author: Mills, Kingston
Type of material:
Journal ArticleCollections
Series/Report no:
European Journal of Immunology;Availability:
Full text availableKeywords:
CD4 TRM cells, Bordetella pertussis, heat-killed Klebsiella pneumoniae (HKKP), Vaccines, Tissue-resident memory T cells, Heterologous immunity, Bacterial immunityDOI:
http://dx.doi.org/10.1002/eji.202250247Metadata
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