NK cell recruitment in salivary glands provides early viral control but is dispensable for tertiary lymphoid structure formation

Elena Pontarini, Davide Lucchesi, Liliane Fossati-Jimack, Rachel Coleby, Paolo Tentorio, Cristina Croia, Michele Bombardieri, Domenico Mavilio

Research output: Contribution to journalArticle

Abstract

Salivary glands (SGs) represent a permissive site for several sialotropic viruses whose persistence is linked to the development of autoimmunity. Natural Killer (NK) cells play a key role in viral clearance but their involvement in viral infection control and in tertiary lymphoid structures (TLS) development within SGs is unknown. By using an inducible model of TLS in the SGs of wild-type C57BL/6 mice, induced by the local delivery of a replication-defective adenovirus (AdV), we demonstrated that circulating NK cells are rapidly recruited to SGs and highly enrich the early inflammatory infiltrate prior to TLS development. NK cells migrating to SGs in response to AdV infection up-regulate NKp46, undergo proliferation, acquire cytotoxic potential, produce Granzyme-B and IFN-γ, and reduce viral load in the acute phase of the infection. Nonetheless, the selective depletion of both circulating and infiltrating NK cells in AdV-infected mice neither affect the development and frequency of TLS nor the onset of autoimmunity. These data demonstrate that, upon local viral delivery of AdV, peripheral NK cells homing to SGs can exert an early control of the viral infection but are dispensable for the formation of TLS and breach of immunologic tolerance.

Original languageEnglish
Pages (from-to)589-602
Number of pages14
JournalJournal of Leukocyte Biology
Volume105
Issue number3
DOIs
Publication statusPublished - Mar 2019

Keywords

  • Adenoviridae/physiology
  • Animals
  • Cell Proliferation
  • Female
  • Immunity, Humoral
  • Killer Cells, Natural/immunology
  • Lymphocytes/pathology
  • Mice, Inbred C57BL
  • Natural Cytotoxicity Triggering Receptor 1/metabolism
  • Salivary Glands/pathology

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