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Infection and Immunity, November 1998, p. 5224-5231, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Resident Enteric Bacteria Are Necessary for Development of Spontaneous Colitis and Immune System Activation in Interleukin-10-Deficient Mice

Rance K. Sellon,1 Susan Tonkonogy,2 Michael Schultz,3 Levinus A. Dieleman,3 Wetonia Grenther,1 Ed Balish,4 Donna M. Rennick,5 and R. Balfour Sartor3,*

Department of Companion Animal and Special Species1 and Department of Microbiology, Pathology and Parasitology, Center for Gastrointestinal Biology and Disease,2 College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606; Division of Digestive Diseases and Nutrition, Department of Medicine and Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina- Chapel Hill, Chapel Hill, North Carolina 27599-70803; and Departments of Surgery and Microbiology, University of Wisconsin, Madison, Wisconsin,4 and Department of Immunology, DNAX Corporation, Palo Alto, California5

Received 25 March 1998/Returned for modification 15 July 1998/Accepted 20 August 1998

Mice with targeted deletion of the gene for interleukin-10 (IL-10) spontaneously develop enterocolitis when maintained in conventional conditions but develop only colitis when kept in specific-pathogen-free (SPF) environments. This study tested the hypothesis that enteric bacteria are necessary for the development of spontaneous colitis and immune system activation in IL-10-deficient mice. IL-10-deficient mice were maintained in either SPF conditions or germfree conditions or were populated with bacteria known to cause colitis in other rodent models. IL-10-deficient mice kept in SPF conditions developed colitis in all segments of the colon (cecum and proximal and distal colon). These mice exhibited immune system activation as evidenced by increased expression of CD44 on CD4+ T cells; increased mesenteric lymph node cell numbers; and increased production of immunoglobulin A (IgA), IgG1, and IL-12 p40 from colon fragment cultures. Mice populated with bacterial strains, including Bacteroides vulgatus, known to induce colitis in other rodent models had minimal colitis. Germfree IL-10-deficient mice had no evidence of colitis or immune system activation. We conclude therefore that resident enteric bacteria are necessary for the development of spontaneous colitis and immune system activation in IL-10-deficient mice.

* Corresponding author. Mailing address: Division of Digestive Diseases and Nutrition, CB # 7080, University of North Carolina, Chapel Hill, NC 27599-7080. Phone: (919) 966-0149. Fax: (919) 966-7468. E-mail: rbs{at}med.unc.edu.

Infection and Immunity, November 1998, p. 5224-5231, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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