Extensive evolutionary and functional diversity among mammalian AIM2-like receptors

نویسندگان

  • Rebecca L. Brunette
  • Janet M. Young
  • Deborah G. Whitley
  • Igor E. Brodsky
  • Harmit S. Malik
  • Daniel B. Stetson
چکیده

Innate immune detection of nucleic acids is important for initiation of antiviral responses. Detection of intracellular DNA activates STING-dependent type I interferons (IFNs) and the ASC-dependent inflammasome. Certain members of the AIM2-like receptor (ALR) gene family contribute to each of these pathways, but most ALRs remain uncharacterized. Here, we identify five novel murine ALRs and perform a phylogenetic analysis of mammalian ALRs, revealing a remarkable diversification of these receptors among mammals. We characterize the expression, localization, and functions of the murine and human ALRs and identify novel activators of STING-dependent IFNs and the ASC-dependent inflammasome. These findings validate ALRs as key activators of the antiviral response and provide an evolutionary and functional framework for understanding their roles in innate immunity.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Evolutionary Analysis of Mammalian ACE2 and the Key Residues Involved in Binding to the Spike Protein Revealed Potential SARS-CoV-2 Hosts

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spilled over to humans via wild mammals, entering the host cell using angiotensin-converting enzyme 2 (ACE2) as receptor through Spike (S) protein binding. While SARS-CoV-2 became fully adapted to humans and globally spread, some mammal species were infected back. The present study evaluated the potential risk of mammals...

متن کامل

Ancient and Recent Selective Pressures Shaped Genetic Diversity at AIM2-Like Nucleic Acid Sensors

AIM2-like receptors (ALRs) are a family of nucleic acid sensors essential for innate immune responses against viruses and bacteria. We performed an evolutionary analysis of ALR genes (MNDA, PYHIN1, IFI16, and AIM2) by analyzing inter- and intraspecies diversity. Maximum-likelihood analyses indicated that IFI16 and AIM2 evolved adaptively in primates, with branch-specific selection at the catarr...

متن کامل

Dp2-Induced Autoantigen/Autoantibody Production From Patients With Systemic Lupus Erythematosus Is Done Through AIM2 And Not NLRP3

Systemic Lupus Erythematosus (SLE) is a disease characterized by the production of autoantibodies against different autoantigens, including double stranded DNA (dsDNA). AIM2 (Protein absent in melanoma 2) is one of the inflammasome proteins which can directly bind to dsDNA. It is therefore possible to speculate that AIM2 may contribute to the disease development of SLE. B cell lines obtained fr...

متن کامل

HLA-KIR Interactions and Immunity to Viral Infections

Host genetic factors play a central role in determining the clinical phenotype of human diseases. Association between two polymorphic loci in human genome, human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptors (KIRs), and genetically complex infectious disease, particularly those of viral etiology, have been historically elusive. Hence, defining the influence of genetic di...

متن کامل

AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA

Cytosolic DNAs derived from retrotransposons serve as pathogen-associated molecular patterns for pattern recognition receptors (PRRs) that stimulate the induction of interferons (IFNs) and other cytokines, leading to autoimmune disease. Cyclic GMP-AMP synthase is one PRR that senses retrotransposon DNA, activating type I IFN responses through the stimulator of IFN genes (STING). Absent in melan...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 209  شماره 

صفحات  -

تاریخ انتشار 2012