LECT2 Protects Mice Against Bacterial Sepsis by Activating Macrophages Via the CD209a Receptor

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2012 Dec 21

PMID 23254286

Citations 51

Authors

Xin-Jiang Lu

Jiong Chen

Chao-Hui Yu

Yu-Hong Shi

Yu-Qing He

Rui-Cheng Zhang

Zuo-An Huang

Ji-Neng Lv

Shun Zhang

Lei Xu

Affiliations

Soon will be listed here.

Abstract

Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine and reduced plasma levels were found in patients with sepsis. However, precise functions and mechanisms of LECT2 remain unclear. The aim of the present study was to determine the role of LECT2 in modulating immune responses using mouse sepsis models. We found that LECT2 treatment improved outcome in mice with bacterial sepsis. Macrophages (MΦ), but not polymorphonuclear neutrophils, mediated the beneficial effect of LECT2 on bacterial sepsis. LECT2 treatment could alter gene expression and enhance phagocytosis and bacterial killing of MΦ in vitro. CD209a was identified to specifically interact with LECT2 and mediate LECT2-induced MΦ activation. CD209a-expressing MΦ was further confirmed to mediate the effect of LECT2 on sepsis in vivo. Our data demonstrate that LECT2 improves protective immunity in bacterial sepsis, possibly as a result of enhanced MΦ functions via the CD209a receptor. The modulation of MΦ functions by LECT2 may serve as a novel potential treatment for sepsis.

Citing Articles

Leukocyte cell-derived chemotaxin 2 (LECT2) regulates liver ischemia-reperfusion injury.

Dong M, Xie Y, Tang Z, Zhao X, Lin F, Zhang G Liver Res. 2025; 8(3):165-171.

PMID: 39957753 PMC: 11771270. DOI: 10.1016/j.livres.2024.09.004.

Role of LECT2 in exacerbating atopic dermatitis: insight from and models via NF-κB signaling pathway.

Liu Z, Jiang X, Zhao K, Ruan H, Ma Y, Ma Y Front Immunol. 2024; 15:1439367.

PMID: 39206203 PMC: 11349537. DOI: 10.3389/fimmu.2024.1439367.

Discovery of Ll-CATH: a novel cathelicidin from the Chong'an Moustache Toad (Leptobrachium liui) with antibacterial and immunomodulatory activity.

Chen J, Zhang C, Wang Y, Zhang L, Seah R, Ma L BMC Vet Res. 2024; 20(1):343.

PMID: 39095814 PMC: 11295328. DOI: 10.1186/s12917-024-04202-9.

Global research trends and hotspots for leukocyte cell-derived chemotaxin-2 from the past to 2023: a combined bibliometric review.

Liu W, Wang Q, Yeerlan J, Yan Y, Xu L, Jia C Front Immunol. 2024; 15:1413466.

PMID: 38881894 PMC: 11176436. DOI: 10.3389/fimmu.2024.1413466.

Elevated serum levels of leukocyte cell-derived chemotaxin 2 are associated with the prevalence of metabolic syndrome.

Zheng X, Lu J, Xiang S, Zou P, Chen H, Liu J Acta Diabetol. 2024; 61(5):643-655.

PMID: 38383671 DOI: 10.1007/s00592-024-02242-z.

References

Garg V, Garg H, Khan A, Trehanpati N, Kumar A, Sharma B . Granulocyte colony-stimulating factor mobilizes CD34(+) cells and improves survival of patients with acute-on-chronic liver failure. Gastroenterology. 2011; 142(3):505-512.e1. DOI: 10.1053/j.gastro.2011.11.027. View

Gros P, Milder F, Janssen B . Complement driven by conformational changes. Nat Rev Immunol. 2007; 8(1):48-58. DOI: 10.1038/nri2231. View

Ong H, Tan P, Wang S, Hian Low D, Ooi L, Hui K . The tumor suppressor function of LECT2 in human hepatocellular carcinoma makes it a potential therapeutic target. Cancer Gene Ther. 2011; 18(6):399-406. DOI: 10.1038/cgt.2011.5. View

Kang Y, Yamazaki S, Iyoda T, Pack M, Bruening S, Kim J . SIGN-R1, a novel C-type lectin expressed by marginal zone macrophages in spleen, mediates uptake of the polysaccharide dextran. Int Immunol. 2003; 15(2):177-86. DOI: 10.1093/intimm/dxg019. View

Levy M, Fink M, Marshall J, Abraham E, Angus D, Cook D . 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003; 31(4):1250-6. DOI: 10.1097/01.CCM.0000050454.01978.3B. View

Hotchkiss R, Karl I . The pathophysiology and treatment of sepsis. N Engl J Med. 2003; 348(2):138-50. DOI: 10.1056/NEJMra021333. View

Yamagoe S, Yamakawa Y, Matsuo Y, Minowada J, Mizuno S, Suzuki K . Purification and primary amino acid sequence of a novel neutrophil chemotactic factor LECT2. Immunol Lett. 1996; 52(1):9-13. DOI: 10.1016/0165-2478(96)02572-2. View

Anderson P, Souza-Moreira L, Morell M, Caro M, OValle F, Gonzalez-Rey E . Adipose-derived mesenchymal stromal cells induce immunomodulatory macrophages which protect from experimental colitis and sepsis. Gut. 2012; 62(8):1131-41. DOI: 10.1136/gutjnl-2012-302152. View

Cohen J . The immunopathogenesis of sepsis. Nature. 2002; 420(6917):885-91. DOI: 10.1038/nature01326. View

10.

White C, Lee J, Kambe T, Fritsche K, Petris M . A role for the ATP7A copper-transporting ATPase in macrophage bactericidal activity. J Biol Chem. 2009; 284(49):33949-56. PMC: 2797165. DOI: 10.1074/jbc.M109.070201. View

11.

Alves-Filho J, Sonego F, Souto F, Freitas A, Verri Jr W, Auxiliadora-Martins M . Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection. Nat Med. 2010; 16(6):708-12. DOI: 10.1038/nm.2156. View

12.

Robinson M, Sancho D, Slack E, LeibundGut-Landmann S, Reis e Sousa C . Myeloid C-type lectins in innate immunity. Nat Immunol. 2006; 7(12):1258-65. DOI: 10.1038/ni1417. View

13.

F Gonzalez S, Lukacs-Kornek V, Kuligowski M, Pitcher L, Degn S, Kim Y . Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes. Nat Immunol. 2010; 11(5):427-34. PMC: 3424101. DOI: 10.1038/ni.1856. View

14.

Chen Q, Chen T, Xu Y, Zhu J, Jiang Y, Zhao Y . Steroid receptor coactivator 3 is required for clearing bacteria and repressing inflammatory response in Escherichia coli-induced septic peritonitis. J Immunol. 2010; 185(9):5444-52. PMC: 3640995. DOI: 10.4049/jimmunol.0903802. View

15.

Ando K, Kato H, Kotani T, Ozaki M, Arimura Y, Yagi J . Plasma leukocyte cell-derived chemotaxin 2 is associated with the severity of systemic inflammation in patients with sepsis. Microbiol Immunol. 2012; 56(10):708-18. DOI: 10.1111/j.1348-0421.2012.00488.x. View

16.

Powlesland A, Ward E, Sadhu S, Guo Y, Taylor M, Drickamer K . Widely divergent biochemical properties of the complete set of mouse DC-SIGN-related proteins. J Biol Chem. 2006; 281(29):20440-9. DOI: 10.1074/jbc.M601925200. View

17.

Kelly-Scumpia K, Scumpia P, Weinstein J, Delano M, Cuenca A, Nacionales D . B cells enhance early innate immune responses during bacterial sepsis. J Exp Med. 2011; 208(8):1673-82. PMC: 3149216. DOI: 10.1084/jem.20101715. View

18.

Xiong W, Knispel R, MacTaggart J, Greiner T, Weiss S, Baxter B . Membrane-type 1 matrix metalloproteinase regulates macrophage-dependent elastolytic activity and aneurysm formation in vivo. J Biol Chem. 2008; 284(3):1765-71. PMC: 2615502. DOI: 10.1074/jbc.M806239200. View

19.

Garcia-Vallejo J, van Kooyk Y . Endogenous ligands for C-type lectin receptors: the true regulators of immune homeostasis. Immunol Rev. 2009; 230(1):22-37. DOI: 10.1111/j.1600-065X.2009.00786.x. View

20.

Kelly-Scumpia K, Scumpia P, Delano M, Weinstein J, Cuenca A, Wynn J . Type I interferon signaling in hematopoietic cells is required for survival in mouse polymicrobial sepsis by regulating CXCL10. J Exp Med. 2010; 207(2):319-26. PMC: 2822595. DOI: 10.1084/jem.20091959. View