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January 2010
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Kate Fitzgerald talks with
ScienceWatch.com and answers a few questions about
this month's Fast Moving Fronts paper in the field of
Immunology. The author has also sent along an image of her
work.
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Article: AIM2 recognizes cytosolic dsDNA and forms a
caspase-1-activating inflammasome with ASC
Authors: Hornung, V;Ablasser, A;Charrel-Dennis, M;Bauernfeind,
F;Horvath, G;Caffrey, DR;Latz, E;Fitzgerald,
KA
Journal: NATURE, 458 (7237): 514-U6 MAR 26 2009
Addresses: Univ Massachusetts, Sch Med, Dept Med, Div Infect
Dis & Immunol, Worcester, MA 01605 USA.
Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis &
Immunol, Worcester, MA 01605 USA.
Pfizer, Cambridge, MA 02139 USA.
Univ Klinikum Bonn, Inst Clin Chem & Pharmacol, D-53127
Bonn, Germany.
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Why do you think your paper is highly
cited?
Innate immunity—immunity that occurs naturally as a result of a
person's genetic constitution or physiology and does not arise from a
previous infection or vaccination—is a fast-paced, exciting field.
Over the last 10 years or so several classes of germline encoded innate
immune receptors have been identified. There are probably not that many
receptors remaining to be defined. We are starting to get a handle on the
full compendium of pattern recognition receptors (PRRs).
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IM2 inflammasome.
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Aim2 (absent in melanoma 2) is one of the last of these to be identified.
Inflammasomes are known to be important in sensing microbial as well as
endogenous danger signals. The discovery of NLR family, pyrin domain
containing 3 (NLRP3) as a mediator of DNA virus-induced inflammation by
Jürg Tschopp and colleagues in the Department of Biochemistry at the
Université de Lausanne in Epalinges, Switzerland, was an exciting
finding. Since then NLRP3 was also shown to detect influenza.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
Yes, the paper describes a new function for a previously studied protein.
Aim2 is known to be induced in cells infected with viruses. Why Aim2 is
elevated in this setting was unclear. Our study indicates that Aim2 is
induced in cells during infection so it can detect DNA from pathogens to
turn on IL-1, an inflammatory cytokine important in ultimately clearing the
infection.
Would you summarize the significance of your paper
in layman's terms?
We identified a receptor which is present in the cytoplasm of cells, a
strategic location to detect microbes which can replicate and spread
through this compartment. Having Aim2 present at this site means there is a
surveillance mechanism in place to sense infection and mount rapid defenses
to eliminate the invading pathogen.
How did you become involved in this research and
were any particular problems encountered along the way?
We became interested in Aim2 as a potential mediator of DNA-induced
inflammation when we looked for proteins in the genome which contained a
pyrin domain (PYD), a domain which mediates protein-protein interactions
with other components of inflammasomes.
Where do you see your research leading in the
future?
We hope to define what role Aim2 plays, not only in host defense to
microbial infection (bacterial, viral, or parasitic), but additionally we
would like to determine if Aim2 contributes to autoimmune diseases, such as
lupus.
Katherine A. Fitzgerald, Ph.D.
Associate Professor of Medicine
University of Massachusetts Medical School
Worcester, MA, USA
Web
KEYWORDS: NF-KAPPA-B; INNATE IMMUNE-RESPONSE; CONTAINING APAF1-LIKE
PROTEIN; REGULATES ACTIVATION; INDUCIBLE GENES; HIN-200 FAMILY; DNA;
CASPASE-1; EXPRESSION; INFECTION.
