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Open Access 01-12-2020 | Research article

The role of CXCR3 and its ligands expression in Brucellar spondylitis

Authors: Xin Hu, Xiaoqian Shang, Liang Wang, Jiahui Fan, Yue Wang, Jie Lv, Shaxika Nazierhan, Hao Wang, Jing Wang, Xiumin Ma

Published in: BMC Immunology | Issue 1/2020

Abstract

Aim

Brucellar spondylitis (BS) is one of the most serious complications of brucellosis. CXCR3 is closely related to the severity of disease infection. This research aimed to study the degree of BS inflammatory damage through analyzing the expression levels of CXCR3 and its ligands (CXCL9 and CXCL10) in patients with BS.

Methods

A total of 29 BS patients and 15 healthy controls were enrolled. Real-Time PCR was used to detect the mRNA expression levels of IFN-γ, CXCR3, CXCL9 and CXCL10 in peripheral blood mononuclear cells (PBMCs) of BS patients and healthy controls. Hematoxylin-Eosin staining was used to show the pathological changes in BS lesion tissues. Immunohistochemistry staining was used to show the protein expression levels of Brucella-Ab, IFN-γ, CXCR3, CXCL9 and CXCL10 in BS lesion tissues. At the same time, ELISA was used to detect the serum levels of IFN-γ, CXCL9 CXCL10 and autoantibodies against CXCR3 in patients with BS.

Results

In lesion tissue of BS patients, it showed necrosis of cartilage, acute or chronic inflammatory infiltration. Brucella-Ab protein was abundantly expressed in close lesion tissue. And the protein expression levels of IFN-γ, CXCR3 and CXCL10 were highly expressed in close lesion tissue and serum of BS patients. At the same time, the mRNA expression levels of IFN-γ, CXCR3 and CXCL10 in PBMCs of BS patients were significantly higher than those in controls.

Conclusion

In our research, the expression levels of IFN-γ, CXCR3 and its ligands were significantly higher than those in controls. It suggested that high expression levels of IFN-γ, CXCR3 and its ligands indicated a serious inflammatory damage in patients with BS.

Unuvar GK, Kilic AU, Doganay M. Current therapeutic strategy in osteoarticular brucellosis. North Clin Istanb. 2019;6(4):415–20. https://doi.org/10.14744/nci.2019.05658.CrossRefPubMedPubMedCentral

Cárdenas L, Awada L, Tizzani P, Cáceres P, Casal J. Characterization and evolution of countries affected by bovine brucellosis (1996-2014). Transbound Emerg Dis. 2019;66(3):1280–90. https://doi.org/10.1111/tbed.13144.CrossRefPubMed

He H, Aishan M, Tai X, Wang Z, Zhang C. Analysis of epidemiological characteristics of human brucellosis in Xinjiang, 2014. Dis Prev Control Bull. 2017;32(02):16–9. https://doi.org/10.13215/j.cnki.jbyfkztb.1607021.CrossRef

Franco MP, Mulder M, Gilman RH, Smits HL. Human brucellosis. Lancet Infect Dis. 2007;7(12):775–86. https://doi.org/10.1016/S1473-3099(07)70286-4.CrossRefPubMed

Tali ET, Koc AM, Oner AY. Spinal brucellosis. Neuroimaging Clin N Am. 2015;25(2):233–45. https://doi.org/10.1016/j.nic.2015.01.004.CrossRefPubMed

Esmaeilnejad-Ganji SM, Esmaeilnejad-Ganji SMR. Osteoarticular manifestations of human brucellosis: a review. World J Orthop. 2019;10(2):54–62. https://doi.org/10.5312/wjo.v10.i2.54.CrossRefPubMedPubMedCentral

Tali ET. Spinal infections. Eur J Radiol. 2004;50(2):120–33. https://doi.org/10.1016/j.ejrad.2003.10.022.CrossRefPubMed

Berchiche YA, Sakmar TP. CXC chemokine receptor 3 alternative splice variants selectively activate different signaling pathways. Mol Pharmacol. 2016;90(4):483–95. https://doi.org/10.1124/mol.116.105502.CrossRefPubMed

Alanio C. Barreira da Silva R, Michonneau D, Bousso P, Ingersoll MA, Albert ML. CXCR3/CXCL10 Axis shapes tissue distribution of memory phenotype CD8(+) T cells in nonimmunized mice. J Immunol. 2018;200(1):139–46. https://doi.org/10.4049/jimmunol.1700564.CrossRefPubMed

10.

Xu G, Zhang P, Dang R, et al. Dynamic changes of Th1 cytokines and the clinical significance of the IFN-γ/TNF-α ratio in acute brucellosis. Mediat Inflamm. 2019;2019:5869257. https://doi.org/10.1155/2019/5869257.CrossRef

11.

Freeman CM, Curtis JL, Chensue SW. CC chemokine receptor 5 and CXC chemokine receptor 6 expression by lung CD8+ cells correlates with chronic obstructive pulmonary disease severity. Am J Pathol. 2007;171(3):767–76. https://doi.org/10.2353/ajpath.2007.061177.CrossRefPubMedPubMedCentral

12.

Pallett LJ, Davies J, Colbeck EJ, et al. IL-2high tissue-resident T cells in the human liver: sentinels for hepatotropic infection. J Exp Med. 2017;214(6):1567–80. https://doi.org/10.1084/jem.20162115.CrossRefPubMedPubMedCentral

13.

Giambartolomei GH, Arriola Benitez PC, Delpino MV. Brucella and Osteoarticular cell activation: partners in crime. Front Microbiol. 2017;8:256. https://doi.org/10.3389/fmicb.2017.00256.CrossRefPubMedPubMedCentral

14.

Liang C, Wei W, Liang X, De E, Zheng B. Spinal brucellosis in Hulunbuir, China, 2011-2016. Infect Drug Resist. 2019;12:1565–71. https://doi.org/10.2147/IDR.S202440.CrossRefPubMedPubMedCentral

15.

Fouskis I, Sandalakis V, Christidou A, Tsatsaris A, Tzanakis N, Tselentis Y, et al. The epidemiology of brucellosis in Greece, 2007-2012: a 'One Health' approach. Trans R Soc Trop Med Hyg. 2018;112(3):124–35. https://doi.org/10.1093/trstmh/try031.CrossRefPubMed

16.

Skendros P, Boura P. Immunity to brucellosis. Rev Sci Tech. 2013;32(1):137–47.CrossRef

17.

Zheng R, Xie S, Niyazi S, Lu X, Sun L, Zhou Y, et al. Meta-analysis of the changes of peripheral blood T cell subsets in patients with brucellosis. J Immunol Res. 2018;2018:8439813. https://doi.org/10.1155/2018/8439813.CrossRefPubMedPubMedCentral

18.

Gheitasi R, Jourghasemi S, Pakzad I, et al. A potential marker in brucellosis, long non coding RNA IFNG-AS1. Mol Biol Rep. 2019;46(6):6495–500. https://doi.org/10.1007/s11033-019-05095-w.CrossRefPubMed

19.

Seiler P, Aichele P, Bandermann S, Hauser AE, Lu B, Gerard NP, et al. Early granuloma formation after aerosol mycobacterium tuberculosis infection is regulated by neutrophils via CXCR3-signaling chemokines. Eur J Immunol. 2003;33:2676–86. https://doi.org/10.1002/eji.200323956.CrossRefPubMed

20.

Van Raemdonck K, Van den Steen PE, Liekens S, Van Damme J, Struyf S. CXCR3 ligands in disease and therapy. Cytokine Growth Factor Rev. 2015;26(3):311–27. https://doi.org/10.1016/j.cytogfr.2014.11.009.CrossRefPubMed

21.

Lee JH, Kim B, Jin WJ, Kim HH, Ha H, Lee ZH. Pathogenic roles of CXCL10 signaling through CXCR3 and TLR4 in macrophages and T cells: relevance for arthritis. Arthritis Res Ther. 2017;19(1):163. https://doi.org/10.1186/s13075-017-1353-6.CrossRefPubMedPubMedCentral

22.

Li CX, Ling CC, Shao Y, et al. CXCL10/CXCR3 signaling mobilized-regulatory T cells promote liver tumor recurrence after transplantation. J Hepatol. 2016;65(5):94–952. https://doi.org/10.1016/j.jhep.2016.05.032.CrossRef

23.

Farber JM. A macrophage mRNA selectively induced by gamma-interferon encodes a member of the platelet factor 4 family of cytokines. Proc Natl Acad Sci U S A. 1990;87(14):5238–42.CrossRef

24.

Luster AD, Unkeless JC, Ravetch JV. Gamma-interferon transcriptionally regulates an early-response gene containing homology to pIatelet proteins. Nature. 1985;315(6021):672–6.CrossRef

Title: The role of CXCR3 and its ligands expression in Brucellar spondylitis
Authors: Xin Hu
Xiaoqian Shang
Liang Wang
Jiahui Fan
Yue Wang
Jie Lv
Shaxika Nazierhan
Hao Wang
Jing Wang
Xiumin Ma
Publication date: 01-12-2020
Publisher: BioMed Central
Published in: BMC Immunology / Issue 1/2020
Electronic ISSN: 1471-2172
DOI: https://doi.org/10.1186/s12865-020-00390-9

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The role of CXCR3 and its ligands expression in Brucellar spondylitis

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