C-type Lectin Mincle Recognizes Glucosyl-diacylglycerol of Streptococcus Pneumoniae and Plays a Protective Role in Pneumococcal Pneumonia

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2016 Dec 7

PMID 27923071

Citations 32

Authors

Friederike Behler-Janbeck

Tomotsugu Takano

Regina Maus

Jennifer Stolper

Danny Jonigk

Meritxell Tort Tarres

Thomas Fuehner

Antje Prasse

Tobias Welte

Mattie S M Timmer

Bridget L Stocker

Yoichi Nakanishi

Tomofumi Miyamoto

Sho Yamasaki

Ulrich A Maus

Affiliations

Soon will be listed here.

Abstract

Among various innate immune receptor families, the role of C-type lectin receptors (CLRs) in lung protective immunity against Streptococcus pneumoniae (S. pneumoniae) is not fully defined. We here show that Mincle gene expression was induced in alveolar macrophages and neutrophils in bronchoalveolar lavage fluids of mice and patients with pneumococcal pneumonia. Moreover, S. pneumoniae directly triggered Mincle reporter cell activation in vitro via its glycolipid glucosyl-diacylglycerol (Glc-DAG), which was identified as the ligand recognized by Mincle. Purified Glc-DAG triggered Mincle reporter cell activation and stimulated inflammatory cytokine release by human alveolar macrophages and alveolar macrophages from WT but not Mincle KO mice. Mincle deficiency led to increased bacterial loads and decreased survival together with strongly dysregulated cytokine responses in mice challenged with focal pneumonia inducing S. pneumoniae, all of which was normalized in Mincle KO mice reconstituted with a WT hematopoietic system. In conclusion, the Mincle-Glc-DAG axis is a hitherto unrecognized element of lung protective immunity against focal pneumonia induced by S. pneumoniae.

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References

Wells C, Salvage-Jones J, Li X, Hitchens K, Butcher S, Murray R . The macrophage-inducible C-type lectin, mincle, is an essential component of the innate immune response to Candida albicans. J Immunol. 2008; 180(11):7404-13. DOI: 10.4049/jimmunol.180.11.7404. View

Paterson G, Orihuela C . Pneumococci: immunology of the innate host response. Respirology. 2010; 15(7):1057-63. PMC: 2956737. DOI: 10.1111/j.1440-1843.2010.01814.x. View

Calbo E, Garau J . Of mice and men: innate immunity in pneumococcal pneumonia. Int J Antimicrob Agents. 2009; 35(2):107-13. DOI: 10.1016/j.ijantimicag.2009.10.002. View

Brumshagen C, Maus R, Bischof A, Ueberberg B, Bohling J, Osterholzer J . FMS-like tyrosine kinase 3 ligand treatment of mice aggravates acute lung injury in response to Streptococcus pneumoniae: role of pneumolysin. Infect Immun. 2012; 80(12):4281-90. PMC: 3497444. DOI: 10.1128/IAI.00854-12. View

Maus U, Backi M, Winter C, Srivastava M, Schwarz M, Ruckle T . Importance of phosphoinositide 3-kinase gamma in the host defense against pneumococcal infection. Am J Respir Crit Care Med. 2007; 175(9):958-66. DOI: 10.1164/rccm.200610-1533OC. View

Wartha F, Beiter K, Albiger B, Fernebro J, Zychlinsky A, Normark S . Capsule and D-alanylated lipoteichoic acids protect Streptococcus pneumoniae against neutrophil extracellular traps. Cell Microbiol. 2007; 9(5):1162-71. DOI: 10.1111/j.1462-5822.2006.00857.x. View

Ishikawa T, Itoh F, Yoshida S, Saijo S, Matsuzawa T, Gonoi T . Identification of distinct ligands for the C-type lectin receptors Mincle and Dectin-2 in the pathogenic fungus Malassezia. Cell Host Microbe. 2013; 13(4):477-88. DOI: 10.1016/j.chom.2013.03.008. View

Schoenen H, Bodendorfer B, Hitchens K, Manzanero S, Werninghaus K, Nimmerjahn F . Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate. J Immunol. 2010; 184(6):2756-60. PMC: 3442336. DOI: 10.4049/jimmunol.0904013. View

Schwandner R, Dziarski R, Wesche H, Rothe M, Kirschning C . Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J Biol Chem. 1999; 274(25):17406-9. DOI: 10.1074/jbc.274.25.17406. View

10.

Feinberg H, Jegouzo S, Rowntree T, Guan Y, Brash M, Taylor M . Mechanism for recognition of an unusual mycobacterial glycolipid by the macrophage receptor mincle. J Biol Chem. 2013; 288(40):28457-65. PMC: 3789947. DOI: 10.1074/jbc.M113.497149. View

11.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

12.

Winter C, Taut K, Langer F, Mack M, Briles D, Paton J . FMS-like tyrosine kinase 3 ligand aggravates the lung inflammatory response to Streptococcus pneumoniae infection in mice: role of dendritic cells. J Immunol. 2007; 179(5):3099-108. DOI: 10.4049/jimmunol.179.5.3099. View

13.

Koppe U, Suttorp N, Opitz B . Recognition of Streptococcus pneumoniae by the innate immune system. Cell Microbiol. 2012; 14(4):460-6. DOI: 10.1111/j.1462-5822.2011.01746.x. View

14.

Werninghaus K, Babiak A, Gross O, Holscher C, Dietrich H, Agger E . Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRgamma-Syk-Card9-dependent innate immune activation. J Exp Med. 2009; 206(1):89-97. PMC: 2626670. DOI: 10.1084/jem.20081445. View

15.

Winter C, Herbold W, Maus R, Langer F, Briles D, Paton J . Important role for CC chemokine ligand 2-dependent lung mononuclear phagocyte recruitment to inhibit sepsis in mice infected with Streptococcus pneumoniae. J Immunol. 2009; 182(8):4931-7. DOI: 10.4049/jimmunol.0804096. View

16.

Endeman H, Meijvis S, Rijkers G, van Velzen-Blad H, van Moorsel C, Grutters J . Systemic cytokine response in patients with community-acquired pneumonia. Eur Respir J. 2010; 37(6):1431-8. DOI: 10.1183/09031936.00074410. View

17.

Steinwede K, Tempelhof O, Bolte K, Maus R, Bohling J, Ueberberg B . Local delivery of GM-CSF protects mice from lethal pneumococcal pneumonia. J Immunol. 2011; 187(10):5346-56. PMC: 3595102. DOI: 10.4049/jimmunol.1101413. View

18.

Amaro R, Liapikou A, Cilloniz C, Gabarrus A, Marco F, Sellares J . Predictive and prognostic factors in patients with blood-culture-positive community-acquired pneumococcal pneumonia. Eur Respir J. 2016; 48(3):797-807. DOI: 10.1183/13993003.00039-2016. View

19.

Adachi O, Kawai T, Takeda K, Matsumoto M, Tsutsui H, Sakagami M . Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity. 1998; 9(1):143-50. DOI: 10.1016/s1074-7613(00)80596-8. View

20.

Rabes A, Zimmermann S, Reppe K, Lang R, Seeberger P, Suttorp N . The C-type lectin receptor Mincle binds to Streptococcus pneumoniae but plays a limited role in the anti-pneumococcal innate immune response. PLoS One. 2015; 10(2):e0117022. PMC: 4319728. DOI: 10.1371/journal.pone.0117022. View