NK cells influence both innate and adaptive immune responses after mucosal immunization with antigen and mucosal adjuvant

Lindsay J. Hall, Simon Clare, Gordon Dougan

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

NK cells were found to be recruited in a temporally controlled manner to the nasal-associated lymphoid tissue and the cervical lymph nodes of mice after intranasal immunization with Ag85B-early secreted antigenic target 6kDa from Mycobacterium tuberculosis mixed with Escherichia coli heat-labile toxin as adjuvant. These NK cells were activated and secreted a diverse range of cytokines and other immunomodulators. Using Ab depletion targeting anti-asialo GM1, we found evidence for altered trafficking, impaired activation, and cytokine secretion of dendritic cells, macrophages, and neutrophils in immunized NK cell-depleted mice compared with control animals. Analysis of Ag-specific immune responses revealed an attenuated Ab and cytokine response in immunized NK cell-depleted animals. Systemic administration of rIL-6 but not rIFN-γ significantly restored immune responses in mice depleted of NK cells. In conclusion, cytokine production, particularly IL-6, via NK cells and NK cell-activated immune populations plays an important role in the establishment of local innate immune responses and the consequent development of adaptive immunity after mucosal immunization.

Original languageEnglish
Pages (from-to)4327-4337
Number of pages11
JournalJournal of Immunology
Volume184
Issue number8
DOIs
StatePublished - 15 Apr 2010
Externally publishedYes

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