Abstract
One of the activating factors of the cells of the innate immune system is the agonists of toll-like receptors (TLRs). Our earlier publications detailed how poly(I:C), a TLR3 agonist, elevates the NK cell population and the associated antigen-specific CD8+ T cell responses. This study involved a single treatment of the B6 mice with poly(I:C) intraperitoneally. To perform a detailed phenotypic analysis, mononuclear cells were prepared from each of the liver, peripheral blood, and spleen. These cells were then examined for their NK cell population by flow cytometric analysis following cell staining with indicated antibodies. The findings of the study showed that the NK cell population of the liver with an NK1.1highCD11bhighCD11chigh B220+Ly6G− phenotype was elevated following the treatment with poly(I:C). In the absence of CD11b molecule (CR3−/− mice), poly(I:C) can still increase the remained numbers of NK cells with NK1.1+CD11b− and NK1.1+Ly6G− phenotypes in the liver while their numbers in the blood decrease. After the treatment with anti-AGM1 Ab, which induced depletion of NK1.1+CD11b+ cells and partial depletion of CD3+NK1.1+ and NK1.1+CD11b− cell populations, poly(I:C) normalized the partial decreases in the numbers of NK cells concomitant with increased numbers of NK1.1−CD11b+ cell population in both liver and blood. Regarding mice with a TLR3−/− phenotype, their injection with poly(I:C) resulted in the partial elevation in the NK cell population as compared to wild-type B6 mice. To summarise, the TLR3 agonist poly(I:C) results in the elevation of a subset of liver NK cells expressing the two myeloid markers CD11c and CD11b. The effect of poly(I:C) on NK cells is partially dependent on TLR3 and independent of the presence of CD11b.
Highlights
Natural killer (NK) cells are immune cells that target and kill cells infected with viruses or tumourigenic cells [1,2,3]
The numbers of NK1.1+CD11b+ cells were reduced in the peripheral blood leukocytes (PBL) (the upper panel of Figure 1(b)) and elevated in the liver (the middle panel of Figure 1(b))
Several studies, including our earlier studies, indicated that the administration of poly(I:C), a TLR3 agonist in vivo, into naïve mice led to the quick rise in NK cell numbers primarily in the liver and that this was linked with greater antitumour effectiveness and antigen-specific reactions [18, 21, 36, 41]
Summary
Natural killer (NK) cells are immune cells that target and kill cells infected with viruses or tumourigenic cells [1,2,3] They are able to differentiate between such cells and normal cells, and spare normal cells [1,2,3]. Other characteristics that are attributed to NK cells include the release of cytokines and chemokines that are vital for the instigation and amplification of an inflammatory response [4,5,6]. Such chemokines and cytokines include TNF-α, IFN-γ, IL-10, GM-CSF, and IL-13 [4,5,6]. Such functions of NK cells may help understand the essential role played by these cells in conducting immune surveillance against tumours and in the eradication of circulating cancer cells in mice [2, 5, 7].
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