Maturation-dependent expression of AIM2 in human B-cells

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.

[1]  O. Levy,et al.  Distinct TLR-mediated cytokine production and immunoglobulin secretion in human newborn naïve B cells , 2016, Innate immunity.

[2]  Si Ming Man,et al.  AIM2 inflammasome in infection, cancer, and autoimmunity: Role in DNA sensing, inflammation, and innate immunity , 2016, European journal of immunology.

[3]  G. Schett,et al.  Interleukin-1 function and role in rheumatic disease , 2016, Nature Reviews Rheumatology.

[4]  Robert A. Carter,et al.  Critical Role for the DNA Sensor AIM2 in Stem Cell Proliferation and Cancer , 2015, Cell.

[5]  Brianne R. Barker,et al.  Inflammasome-independent role of AIM2 in suppressing colon tumorigenesis via DNA-PK and Akt , 2015, Nature Medicine.

[6]  B. Chiang,et al.  Sex-dependent differential activation of NLRP3 and AIM2 inflammasomes in SLE macrophages. , 2015, Rheumatology.

[7]  M. Pichichero,et al.  Immune responses in neonates , 2014, Expert review of clinical immunology.

[8]  B. Jacobsson,et al.  TLR3 impairment in human newborns , 2013, Journal of leukocyte biology.

[9]  D. Choubey,et al.  IFI16 Protein Mediates the Anti-inflammatory Actions of the Type-I Interferons through Suppression of Activation of Caspase-1 by Inflammasomes , 2011, PloS one.

[10]  V. Hornung,et al.  Cytosolic DNA Triggers Inflammasome Activation in Keratinocytes in Psoriatic Lesions , 2011, Science Translational Medicine.

[11]  Pedro Romero,et al.  Type I interferon inhibits interleukin-1 production and inflammasome activation. , 2011, Immunity.

[12]  A. Bowie,et al.  IFI16 is an innate immune sensor for intracellular DNA , 2010, Nature Immunology.

[13]  G. Superti-Furga,et al.  An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome , 2009, Nature Immunology.

[14]  Jasmyn A. Dunn,et al.  HIN-200 Proteins Regulate Caspase Activation in Response to Foreign Cytoplasmic DNA , 2009, Science.

[15]  E. Alnemri,et al.  AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA , 2009, Nature.

[16]  Daniel R. Caffrey,et al.  AIM2 recognizes cytosolic dsDNA and forms a caspase-1 activating inflammasome with ASC , 2009, Nature.

[17]  F. Lund Cytokine-producing B lymphocytes-key regulators of immunity. , 2008, Current opinion in immunology.

[18]  Ofer Levy,et al.  Innate immunity of the newborn: basic mechanisms and clinical correlates , 2007, Nature Reviews Immunology.

[19]  G. Hortobagyi,et al.  AIM2 suppresses human breast cancer cell proliferation in vitro and mammary tumor growth in a mouse model , 2006, Molecular Cancer Therapeutics.

[20]  Ruslan Medzhitov,et al.  Control of B-cell responses by Toll-like receptors , 2005, Nature.

[21]  H. Xin,et al.  Cytoplasmic localization of the interferon‐inducible protein that is encoded by the AIM2 (absent in melanoma) gene from the 200‐gene family , 2000, FEBS letters.

[22]  C. Morimoto,et al.  B cell subpopulations separated by CD27 and crucial collaboration of CD27+ B cells and helper T cells in immunoglobulin production , 1997, European journal of immunology.