Abstract
BackgroundNatural killer (NK) cells in the upper respiratory airways are not well characterized. In the current study, we sought to characterize and functionally assess murine nasal NK cells.MethodsUsing immunohistochemistry and flow cytometry, we compared the nasal NK cells of Ncr1 GFP/+ knock-in mice, whose NK cells produced green fluorescent protein, with their splenic and pulmonary counterparts. In addition, we functionally analyzed the nasal NK cells of these mice in vitro. To assess the in vivo functions of nasal NK cells, C57BL/6 mice depleted of NK cells after treatment with PK136 antibody were nasally infected with influenza virus PR8.ResultsImmunohistochemical analysis confirmed the presence of NK cells in the lamina propria of nasal mucosa, and flow cytometry showed that these cells were of NK cell lineage. The expression patterns of Ly49 receptor, CD11b/CD27, CD62L and CD69 revealed that nasal NK cells had an immature and activated phenotype compared with that of their splenic and pulmonary counterparts. Effector functions including degranulation and IFN(interferon)-γ production after in vitro stimulation with phorbol 12-myristate-13-acetate plus ionomycin or IL(interleukin)-12 plus IL-18 were dampened in nasal NK cells, and the depletion of NK cells led to an increased influenza virus titer in nasal passages.ConclusionsThe NK cells of the murine nasal passage belong to the conventional NK cell linage and characteristically demonstrate an immature and activated phenotype. Despite their hyporesponsiveness in vitro, nasal NK cells play important roles in the host defense against nasal influenza virus infection.
Highlights
Natural killer (NK) cells play important roles in host immune defense and have anti-tumor activity: they produce cytotoxic granules containing molecules such as perforins and granzymes to lyse infected or neoplastic cells [1]
Immunohistochemical analysis confirmed the presence of NK cells in the lamina propria of nasal mucosa, and flow cytometry showed that these cells were of NK cell lineage
The expression patterns of Ly49 receptor, CD11b/CD27, CD62L and CD69 revealed that nasal NK cells had an immature and activated phenotype compared with that of their splenic and pulmonary counterparts
Summary
Natural killer (NK) cells play important roles in host immune defense and have anti-tumor activity: they produce cytotoxic granules containing molecules such as perforins and granzymes to lyse infected or neoplastic cells [1]. CD11clowB220+ IFN-producing cells were originally considered to be killer dendritic cells but are known to be activated NK cells that can produce various IFNs [4, 5]. These and similar investigations of mucosal NK cells helped to establish the concept of innate lymphoid cells (ILCs) [6]. We sought to characterize and functionally assess murine nasal NK cells
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