Published online
doi:10.1084/jem.20070563
The Journal of Experimental Medicine, Vol. 204, No. 8, 1891-1900
The Rockefeller University Press, 0022-1007 $30.00
© Brandl et al.
MyD88-mediated signals induce the bactericidal lectin RegIII
and protect mice against intestinal Listeria monocytogenes infection
Katharina Brandl1,
George Plitas2,
Bernd Schnabl3,
Ronald P. DeMatteo2, and
Eric G. Pamer1
1 Infectious Diseases Service, Department of Medicine, Immunology Program, Sloan-Kettering Institute, 2 Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021
3 Department of Medicine, Columbia University, New York, NY 10032
Listeria monocytogenes is a food-borne bacterial pathogen that causes systemic infection by traversing the intestinal mucosa. Although MyD88-mediated signals are essential for defense against systemic L. monocytogenes infection, the role of Toll-like receptor and MyD88 signaling in intestinal immunity against this pathogen has not been defined. We show that clearance of L. monocytogenes from the lumen of the distal small intestine is impaired in MyD88–/– mice. The distal ileum of wild-type (wt) mice expresses high levels of RegIII
, which is a bactericidal lectin that is secreted into the bowel lumen, whereas RegIII
expression in MyD88–/– mice is nearly undetectable. In vivo depletion of RegIII
from the small intestine of wt mice diminishes killing of luminal L. monocytogenes, whereas reconstitution of MyD88-deficient mice with recombinant RegIII
enhances intestinal bacterial clearance. Experiments with bone marrow chimeric mice reveal that MyD88-mediated signals in nonhematopoietic cells induce RegIII
expression in the small intestine, thereby enhancing bacterial killing. Our findings support a model of MyD88-mediated epithelial conditioning that protects the intestinal mucosa against bacterial invasion by inducing RegIII
.
Abbreviations used: Defcr, Defensin-related cryptdin; LLO, listeriolysin O; MLN, mesenteric lymph node; p.i., post-infection; TLR, Toll-like receptor; rs, related sequence.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Facebook
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:
-
Deckert, M., Schluter, D.
(2009). Comment on "Critical Roles of NK and CD8+ T Cells in Central Nervous System Listeriosis". J. Immunol.
183: 5437-5437
[Full Text]
-
Petnicki-Ocwieja, T., Hrncir, T., Liu, Y.-J., Biswas, A., Hudcovic, T., Tlaskalova-Hogenova, H., Kobayashi, K. S.
(2009). Nod2 is required for the regulation of commensal microbiota in the intestine. Proc. Natl. Acad. Sci. USA
106: 15813-15818
[Abstract]
[Full Text]
-
Dessein, R, Gironella, M, Vignal, C, Peyrin-Biroulet, L, Sokol, H, Secher, T, Lacas-Gervais, S, Gratadoux, J-J, Lafont, F, Dagorn, J-C, Ryffel, B, Akira, S, Langella, P, Nunez, G, Sirard, J-C, Iovanna, J, Simonet, M, Chamaillard, M
(2009). Toll-like receptor 2 is critical for induction of Reg3{beta} expression and intestinal clearance of Yersinia pseudotuberculosis. Gut
58: 771-776
[Abstract]
[Full Text]
-
Brandl, K., Rutschmann, S., Li, X., Du, X., Xiao, N., Schnabl, B., Brenner, D. A., Beutler, B.
(2009). Enhanced sensitivity to DSS colitis caused by a hypomorphic Mbtps1 mutation disrupting the ATF6-driven unfolded protein response. Proc. Natl. Acad. Sci. USA
106: 3300-3305
[Abstract]
[Full Text]
-
Mukherjee, S., Partch, C. L., Lehotzky, R. E., Whitham, C. V., Chu, H., Bevins, C. L., Gardner, K. H., Hooper, L. V.
(2009). Regulation of C-type Lectin Antimicrobial Activity by a Flexible N-terminal Prosegment. J. Biol. Chem.
284: 4881-4888
[Abstract]
[Full Text]
-
Hattori, M., Taylor, T. D.
(2009). The Human Intestinal Microbiome: A New Frontier of Human Biology. DNA Res
16: 1-12
[Abstract]
[Full Text]
-
Vaishnava, S., Behrendt, C. L., Ismail, A. S., Eckmann, L., Hooper, L. V.
(2008). Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc. Natl. Acad. Sci. USA
105: 20858-20863
[Abstract]
[Full Text]
-
Toledo, C. C., Rogers, T. J., Svensson, M., Tati, R., Fischer, H., Svanborg, C., Karpman, D.
(2008). Shiga Toxin-Mediated Disease in MyD88-Deficient Mice Infected with Escherichia coli O157:H7. Am. J. Pathol.
173: 1428-1439
[Abstract]
[Full Text]
-
Pamer, E. G.
(2008). TLR Polymorphisms and the Risk of Invasive Fungal Infections. NEJM
359: 1836-1838
[Full Text]