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Infection and Immunity, April 2005, p. 2312-2320, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2312-2320.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mouse Paneth Cell Secretory Responses to Cell Surface Glycolipids of Virulent and Attenuated Pathogenic Bacteria

Hiroki Tanabe,^1, Tokiyoshi Ayabe,^1, Brian Bainbridge,² Tina Guina,^3,4 Robert K. Ernst,^3,4 Richard P. Darveau,² Samuel I. Miller,^3,4 and Andre J. Ouellette^1,5*

Departments of Pathology,¹ Microbiology and Molecular Genetics, School of Medicine, College of Health Sciences, University of California, Irvine, California,⁵ Departments of Periodontics,² Microbiology,³ Medicine, University of Washington, Seattle, Washington⁴

Received 28 May 2004/ Returned for modification 19 July 2004/ Accepted 16 November 2004

Mouse Paneth cells respond to bacteria and bacterial cell surface antigens by discharging secretory granules into the lumen of small intestinal crypts (T. Ayabe et al., Nat. Immunol. 1:113-118, 2000). To investigate mechanisms regulating these responses, purified surface glycolipid molecules with known acyl chain modifications and attenuated properties were tested for the ability to stimulate Paneth cell secretion. The antigens included lipopolysaccharide (LPS) from wild-type and msbB-null Escherichia coli and phoP-null and phoP-constitutive Salmonella enterica serovar Typhimurium strains, as well as LPS, lipid A, and lipoteichoic acid from Pseudomonas aeruginosa and Listeria monocytogenes grown in Mg²⁺-limited media. Measurements of total secreted protein, secreted lysozyme, and the bactericidal peptide activities of collected secretions showed that the purified antigens elicited similar secretory responses from Paneth cells in mouse crypts ex vivo, regardless of glycolipid acyl chain modification. Despite their impaired Tlr4 pathway, Paneth cells in ex vivo C3H/HeJ mouse crypts released equivalent amounts of bactericidal peptide activity in response to purified bacterial antigens, including lipid A. Thus, mouse Paneth cells respond equivalently to purified bacterial cell envelope glycolipids, regardless of functional Tlr4, the structural properties of glycolipid acyl chains, or their association with virulence in humans.

Editor: F. C. Fang

Present address: Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Hokkaido, Japan.

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