Innate immunity and arthritis: Neutrophil Rac and toll-like receptor 4 expression define outcomes in infection-triggered arthritis

Sean Xiang Zhang, Michael Glogauer, Fei Zhu, Tae Hwan Kim, Basil Chiu, Robert D. Inman

Research output: Contribution to journalArticle

Abstract

Objective. The role of innate immunity in Chlamydia-induced arthritis has not been defined. The purpose of this study was to examine the role of neutrophils in experimental arthritis in mice with targeted elimination of the small GTPases Rac1 and Rac2, as well as the role of Toll-like receptors (TLRs) in this model. Methods. Arthritis was induced by intraarticular inoculation of synoviocyte-packaged Chlamydia trachomatis. The degree of arthritis was assessed according to joint swelling and pathology scores. The persistence of Chlamydia in joints was assessed by immunoassay. The expression of TLR-2 and TLR-4 in neutrophils was detected by semiquantitative reverse transcription-polymerase chain reaction. Results. In the acute phase, wild-type mice developed more severe arthritis than did Rac-deficient mice, with abundant infiltration of neutrophils into the joint. In the chronic phase, the Rac-deficient mice developed more severe arthritis and demonstrated defective clearance of the pathogen from the joint. In vitro stimulation of neutrophils with Chlamydia up-regulated the expression of TLR-4, but not TLR-2, in wild-type mice. However, neutrophils from Rac-deficient mice did not show this up-regulation of TLR-4. Sustained TLR-4 expression in neutrophils was found to be dependent on the expression of Rac. Mice genetically deficient in TLR-4 demonstrated more severe arthritis than did the controls. Thus, Rac expression plays a profound role in infection-triggered arthritis and demonstrates a bimodal influence on the disease process, exacerbating acute joint inflammation but controlling chronic arthritis. Rac deficiency was associated with diminished TLR-4 expression, impaired host clearance of the pathogen, and more severe chronic arthritis. Conclusion. In infection-triggered arthritis, innate immunity plays a critical role. Effective host clearance of an arthritogenic pathogen depends on intact expression of Rac and appropriate expression of TLR-4 by neutrophils.

Original languageEnglish (US)
Pages (from-to)1297-1304
Number of pages8
JournalArthritis and Rheumatism
Volume52
Issue number4
DOIs
StatePublished - Apr 2005
Externally publishedYes

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Toll-Like Receptor 4
Innate Immunity
Arthritis
Neutrophils
Infection
Joints
Chlamydia
Toll-Like Receptor 2
Experimental Arthritis
Monomeric GTP-Binding Proteins
Neutrophil Infiltration
Toll-Like Receptors
Chlamydia trachomatis
Immunoassay
Reverse Transcription
Up-Regulation
Pathology
Inflammation
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Innate immunity and arthritis : Neutrophil Rac and toll-like receptor 4 expression define outcomes in infection-triggered arthritis. / Zhang, Sean Xiang; Glogauer, Michael; Zhu, Fei; Kim, Tae Hwan; Chiu, Basil; Inman, Robert D.

In: Arthritis and Rheumatism, Vol. 52, No. 4, 04.2005, p. 1297-1304.

Research output: Contribution to journalArticle

Zhang, Sean Xiang ; Glogauer, Michael ; Zhu, Fei ; Kim, Tae Hwan ; Chiu, Basil ; Inman, Robert D. / Innate immunity and arthritis : Neutrophil Rac and toll-like receptor 4 expression define outcomes in infection-triggered arthritis. In: Arthritis and Rheumatism. 2005 ; Vol. 52, No. 4. pp. 1297-1304.
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abstract = "Objective. The role of innate immunity in Chlamydia-induced arthritis has not been defined. The purpose of this study was to examine the role of neutrophils in experimental arthritis in mice with targeted elimination of the small GTPases Rac1 and Rac2, as well as the role of Toll-like receptors (TLRs) in this model. Methods. Arthritis was induced by intraarticular inoculation of synoviocyte-packaged Chlamydia trachomatis. The degree of arthritis was assessed according to joint swelling and pathology scores. The persistence of Chlamydia in joints was assessed by immunoassay. The expression of TLR-2 and TLR-4 in neutrophils was detected by semiquantitative reverse transcription-polymerase chain reaction. Results. In the acute phase, wild-type mice developed more severe arthritis than did Rac-deficient mice, with abundant infiltration of neutrophils into the joint. In the chronic phase, the Rac-deficient mice developed more severe arthritis and demonstrated defective clearance of the pathogen from the joint. In vitro stimulation of neutrophils with Chlamydia up-regulated the expression of TLR-4, but not TLR-2, in wild-type mice. However, neutrophils from Rac-deficient mice did not show this up-regulation of TLR-4. Sustained TLR-4 expression in neutrophils was found to be dependent on the expression of Rac. Mice genetically deficient in TLR-4 demonstrated more severe arthritis than did the controls. Thus, Rac expression plays a profound role in infection-triggered arthritis and demonstrates a bimodal influence on the disease process, exacerbating acute joint inflammation but controlling chronic arthritis. Rac deficiency was associated with diminished TLR-4 expression, impaired host clearance of the pathogen, and more severe chronic arthritis. Conclusion. In infection-triggered arthritis, innate immunity plays a critical role. Effective host clearance of an arthritogenic pathogen depends on intact expression of Rac and appropriate expression of TLR-4 by neutrophils.",
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AB - Objective. The role of innate immunity in Chlamydia-induced arthritis has not been defined. The purpose of this study was to examine the role of neutrophils in experimental arthritis in mice with targeted elimination of the small GTPases Rac1 and Rac2, as well as the role of Toll-like receptors (TLRs) in this model. Methods. Arthritis was induced by intraarticular inoculation of synoviocyte-packaged Chlamydia trachomatis. The degree of arthritis was assessed according to joint swelling and pathology scores. The persistence of Chlamydia in joints was assessed by immunoassay. The expression of TLR-2 and TLR-4 in neutrophils was detected by semiquantitative reverse transcription-polymerase chain reaction. Results. In the acute phase, wild-type mice developed more severe arthritis than did Rac-deficient mice, with abundant infiltration of neutrophils into the joint. In the chronic phase, the Rac-deficient mice developed more severe arthritis and demonstrated defective clearance of the pathogen from the joint. In vitro stimulation of neutrophils with Chlamydia up-regulated the expression of TLR-4, but not TLR-2, in wild-type mice. However, neutrophils from Rac-deficient mice did not show this up-regulation of TLR-4. Sustained TLR-4 expression in neutrophils was found to be dependent on the expression of Rac. Mice genetically deficient in TLR-4 demonstrated more severe arthritis than did the controls. Thus, Rac expression plays a profound role in infection-triggered arthritis and demonstrates a bimodal influence on the disease process, exacerbating acute joint inflammation but controlling chronic arthritis. Rac deficiency was associated with diminished TLR-4 expression, impaired host clearance of the pathogen, and more severe chronic arthritis. Conclusion. In infection-triggered arthritis, innate immunity plays a critical role. Effective host clearance of an arthritogenic pathogen depends on intact expression of Rac and appropriate expression of TLR-4 by neutrophils.

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