Double-stranded RNA of intestinal commensal bacteria triggers production of protective IFN-β
Tadaomi
Kawashima1, 2,
Huimin
Yan1, 3,
Zijin
Guo4,
Joaquim
Carreras1, 5,
Ryosuke
Uchiyama6,
Ryutaro
Fukui7,
Tsuneyasu
Kaisho8,
Shizuo
Akira8,
Kensuke
Miyake7,
Hiroko
Tsutsui6,
Takashi
Saito4 and
Noriko
M.
Tsuji1*
-
1
National Institute of Advanced Science and Technology, Biomedical Research Institute, Japan
-
2
Kikkoman Corporation, Japan
-
3
The Fifth Hospital of Shijiazhuang, China
-
4
RIKEN, Japan
-
5
Tokai University, Japan
-
6
Hyogo College of Medicine, Japan
-
7
The University of Tokyo, The Institute of Medical Science, Japan
-
8
Osaka University, WPI Immunology Frontier Research Center, Japan
The small intestine harbors a substantial number of commensal bacteria and is sporadically invaded by pathogens, but the response to these microorganisms is fundamentally different. We identified a discriminatory sensor using Toll-like receptor 3 (TLR3). Double-stranded RNA (dsRNA) of one major commensal species, lactic acid bacteria (LAB), triggered IFN-β production from dendritic cells (DCs) and protected mice from experimental colitis. Endosomal TLRs are required for this protective mechanism, because Tlr3-/- as well as Unc93b13d mice, in which endosomal TLR3, 7, and 9 are dysfunctional, were not affected by oral administration of LAB in colitis model. While digestion of dsRNA canceled in vivo effects, suggesting TLR3 initiates the anti-inflammatory process, we also found that cooperation of TLR3 and TLR9 maximized IFN-β production in vitro. Compared to LAB, pathogenic bacteria contained less dsRNA and induced much less IFN-β. Moreover, dsRNA was not involved in pathogen-induced IFN-β induction. These results identify TLR3 as a sensor to small intestinal commensal bacteria and contribute to the maintenance of immunological homeostasis.
Collaborators: Daisuke Kaneko, Ikuko Nishimura
Keywords:
TLR3,
endosome,
small intestine,
anti-inflammation,
Colitis,
Lactic acid bacteria,
IFN-beta,
double-stranded RNA
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Host-pathogen interactions
Citation:
Kawashima
T,
Yan
H,
Guo
Z,
Carreras
J,
Uchiyama
R,
Fukui
R,
Kaisho
T,
Akira
S,
Miyake
K,
Tsutsui
H,
Saito
T and
Tsuji
NM
(2013). Double-stranded RNA of intestinal commensal bacteria triggers production of protective IFN-β.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01140
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Received:
20 Aug 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Noriko M Tsuji, National Institute of Advanced Science and Technology, Biomedical Research Institute, Tsukuba, Ibaraki, 305-0046, Japan, tsuji.noriko@nihon-u.ac.jp