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Impaired immunity to intestinal bacterial infection in stromelysin-1 (matrix metalloproteinase-3)-deficient mice

Impaired immunity to intestinal bacterial infection in stromelysin-1 (matrix metalloproteinase-3)-deficient mice
Impaired immunity to intestinal bacterial infection in stromelysin-1 (matrix metalloproteinase-3)-deficient mice
Infection of mice with the intestinal bacterial pathogen Citrobacter rodentium results in colonic mucosal hyperplasia and a local Th1 inflammatory response similar to that seen in mouse models of inflammatory bowel disease. Matrix metalloproteinases (MMPs) have been shown to mediate matrix remodeling and cell migration during tissue injury and repair in the intestine. We have previously shown enhanced pathology in infected TNFRp55?/?, IL-12p40?/?, and IFN- ?/? mice, and here we show that this is associated with an increase in stromelysin-1 (MMP3) transcripts in colonic tissues.
We have therefore investigated the role of MMP3 in colonic mucosal hyperplasia and the local Th1 responses using MMP3?/? mice. In MMP3?/? mice, similar mucosal thickening was observed after infection as in wild-type (WT) mice. Colonic tissues from MMP3?/? mice showed a compensatory increase in the expression of other MMP transcripts, such as MMP7 and MMP12. However, MMP3?/? mice showed delayed clearance of bacteria and delayed appearance of CD4? T lymphocytes into intestinal lamina propria. CSFE-labeled mesenteric lymph node CD4? T lymphocytes from infected WT mice migrated in fewer numbers into the mesenteric lymph nodes and colon of MMP3?/? mice than into those of WT mice. These studies show that mucosal remodeling can occur in the absence of MMP3, but that MMP3 plays a role in the migration of CD4? T lymphocytes to the intestinal mucosa.
0022-1767
5171-5179
Li, Chris K.F.
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Pender, Sylvia L.F.
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Pickard, Karen M.
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Chance, Victoria
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Holloway, Judith A.
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Huett, Alan
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Gonçalves, Nathalie S.
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Mudgett, John S.
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Dougan, Gordon
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Frankel, Gad
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MacDonald, Thomas T.
a6bde8a9-acc4-4128-851f-dd5dbfe28816
Li, Chris K.F.
dfe61de8-c2a2-47ef-89a8-1d15aa15b10c
Pender, Sylvia L.F.
62528b03-ec42-41bb-80fe-48454c2c5242
Pickard, Karen M.
e5188669-dff1-49c7-9c6f-8122b0c74bd9
Chance, Victoria
d1561cca-854b-422c-8971-5d1f8f68c4e0
Holloway, Judith A.
f22f45f3-6fc8-4a4c-bc6c-24add507037c
Huett, Alan
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Gonçalves, Nathalie S.
0043456b-1123-4a73-8661-decee839e9c7
Mudgett, John S.
a2a3e67a-3d0e-40ca-a5a2-fc877f004d4a
Dougan, Gordon
71c21614-43d2-47f8-b6b4-342794c74342
Frankel, Gad
50b087e6-23cb-465d-b1b9-1152b6d574e0
MacDonald, Thomas T.
a6bde8a9-acc4-4128-851f-dd5dbfe28816

Li, Chris K.F., Pender, Sylvia L.F., Pickard, Karen M., Chance, Victoria, Holloway, Judith A., Huett, Alan, Gonçalves, Nathalie S., Mudgett, John S., Dougan, Gordon, Frankel, Gad and MacDonald, Thomas T. (2004) Impaired immunity to intestinal bacterial infection in stromelysin-1 (matrix metalloproteinase-3)-deficient mice. Journal of Immunology, 173 (8), 5171-5179.

Record type: Article

Abstract

Infection of mice with the intestinal bacterial pathogen Citrobacter rodentium results in colonic mucosal hyperplasia and a local Th1 inflammatory response similar to that seen in mouse models of inflammatory bowel disease. Matrix metalloproteinases (MMPs) have been shown to mediate matrix remodeling and cell migration during tissue injury and repair in the intestine. We have previously shown enhanced pathology in infected TNFRp55?/?, IL-12p40?/?, and IFN- ?/? mice, and here we show that this is associated with an increase in stromelysin-1 (MMP3) transcripts in colonic tissues.
We have therefore investigated the role of MMP3 in colonic mucosal hyperplasia and the local Th1 responses using MMP3?/? mice. In MMP3?/? mice, similar mucosal thickening was observed after infection as in wild-type (WT) mice. Colonic tissues from MMP3?/? mice showed a compensatory increase in the expression of other MMP transcripts, such as MMP7 and MMP12. However, MMP3?/? mice showed delayed clearance of bacteria and delayed appearance of CD4? T lymphocytes into intestinal lamina propria. CSFE-labeled mesenteric lymph node CD4? T lymphocytes from infected WT mice migrated in fewer numbers into the mesenteric lymph nodes and colon of MMP3?/? mice than into those of WT mice. These studies show that mucosal remodeling can occur in the absence of MMP3, but that MMP3 plays a role in the migration of CD4? T lymphocytes to the intestinal mucosa.

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Published date: 15 October 2004

Identifiers

Local EPrints ID: 27230
URI: http://eprints.soton.ac.uk/id/eprint/27230
ISSN: 0022-1767
PURE UUID: b8b689f8-aa55-40a6-89e8-a934c955c69f
ORCID for Sylvia L.F. Pender: ORCID iD orcid.org/0000-0001-6332-0333
ORCID for Judith A. Holloway: ORCID iD orcid.org/0000-0002-2268-3071

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Date deposited: 27 Apr 2006
Last modified: 16 Mar 2024 03:19

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Contributors

Author: Chris K.F. Li
Author: Karen M. Pickard
Author: Victoria Chance
Author: Alan Huett
Author: Nathalie S. Gonçalves
Author: John S. Mudgett
Author: Gordon Dougan
Author: Gad Frankel
Author: Thomas T. MacDonald

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