Abstract
Intracellular DNA- and RNA-sensing receptors, such as the IFN-inducible protein Absent in Melanoma 2 (AIM2), serve as host sensors against a wide range of infections. Immune sensing and inflammasome activation by AIM2 has been implicated in innate antiviral recognition in many experimental systems using cell-lines and animal models. However, little is known about the expression and function of AIM2 in freshly isolated human cells. In this study we investigated the expression of AIM2 in different cell types derived from human cord and adult peripheral blood, in steady state and following in vitro-activation. Adult but not cord blood B-cells expressed high levels of AIM2 mRNA at steady state. In adults, AIM2 was primarily expressed in mature memory CD27+ B-cells. Both adult and cord blood derived B-cells could induce their transcription of AIM2 mRNA in response to type II IFN but not type I IFN or the AIM2 ligand poly dA:dT. Upon B-cell receptor stimulation, B-cells from adult blood expressed reduced levels of AIM2 mRNA. In addition, we show that adult B-cells were able to release IL-1β upon stimulation with synthetic DNA. We conclude that functional AIM2 is preferentially expressed in adult human CD27+ B-cells, but is absent in cord blood mononuclear cells.
Highlights
The innate human immune system is equipped with a variety of pattern recognition receptors (PRRs) that are able to sense the presence of nucleic acids
A more detailed analysis of different mononuclear cells (B-cells, NK cells, CD4+ T-cells, CD8+ T-cells, plasmacytoid DC (pDC), myeloid DC (myDC) and monocytes) revealed that absent in melanoma 2 (AIM2) was preferentially expressed in adult B-cells (Fig 1B), whereas other mononuclear cells derived from both cord and adult blood expressed no, or low, levels of AIM2 (Fig 1B and S2 Fig)
In this paper we show that adult but not cord blood mononuclear cells express AIM2
Summary
The innate human immune system is equipped with a variety of pattern recognition receptors (PRRs) that are able to sense the presence of nucleic acids. Among these are the inflammasome receptor proteins that upon binding to its ligand form the inflammasome. The most commonly discussed PPRs that are able to form inflammasomes includes the nucleotide-binding domain, leucine-rich repeat containing proteins (NLRs) and the absent in melanoma 2 (AIM2) like receptors (ALRs) (i.e. the PYHIN-family). The ALRs include the DNA sensors IFI16 and AIM2 that both recognize double stranded DNA (dsDNA) inside the cell. IFI16 can sence the presence of dsDNA in both the cytoplasm and the nucleus, whereas AIM2 sense dsDNA that is located in the cytoplasm [1,2,3,4].
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