Abstract
The high morbi-mortality associated with invasive candidiasis (IC) is a persistent problem in hospitals. Mannose-binding lectin (MBL) plays a role in innate immunity through its interaction with mannosylated molecules of Candida albicans. A correlation between MBL deficiency and vulvovaginal candidiasis or peritonitis has been reported. We investigated circulating MBL levels and their evolution during the course of IC. Sixty-eight patients with proven IC, 82 hospitalized patients (HP) without evidence of infection, and 70 healthy subjects (HS) were studied in order to examine the relationship between serum MBL and IC. Serum MBL levels were measured by enzyme-linked immunosorbent assay (ELISA). MBL levels were significantly higher in IC patients than in HP and HS (p < 0.0001, p < 0.0055, respectively). A change in MBL concentrations was observed during the course of IC, with a dramatic decrease during the 2 days before positive blood culture sampling. This decrease was concomitant with the presence of high levels of circulating mannan (Mn). Like MBL levels, anti-mannan antibodies (AMn) increased after the mannanemia/blood culture period. These findings suggest a possible role of MBL during the early stage of IC. The mechanisms that regulate these observations in terms of effect and consequences on innate and adaptive immunity and the prognosis of IC require further investigation.
Similar content being viewed by others
References
Miceli MH, Diaz JA, Lee SA. Emerging opportunistic yeast infections. Lancet Infect Dis. 2011;11:142–51.
Sendid B, Cotteau A, Francois N, D’Haveloose A, Standaert A, Camus D, Poulain D. Candidaemia and antifungal therapy in a French University Hospital: rough trends over a decade and possible links. BMC Infect Dis. 2006;6:80.
Eggimann P, Garbino J, Pittet D. Management of Candida species infections in critically ill patients. Lancet Infect Dis. 2003;3:772–85.
Fujita T. Evolution of the lectin-complement pathway and its role in innate immunity. Nat Rev Immunol. 2002;2:346–53.
Ip WK, Takahashi K, Ezekowitz RA, Stuart LM. Mannose-binding lectin and innate immunity. Immunol Rev. 2009;230:9–21.
Minchinton RM, Dean MM, Clark TR, Heatley S, Mullighan CG. Analysis of the relationship between mannose-binding lectin (MBL) genotype. MBL levels and function in an Australian blood donor population Scand J Immunol. 2002;56:630–41.
Ytting H, Christensen IJ, Thiel S, Jensenius JC, Svendsen MN, Nielsen L, Lottenburger T, Nielsen HJ. Biological variation in circulating levels of mannan-binding lectin (MBL) and MBL-associated serine protease-2 and the influence of age, gender and physical exercise. Scand J Immunol. 2007;66:458–64.
Thiel S, Frederiksen PD, Jensenius JC. Clinical manifestations of mannan-binding lectin deficiency. Mol Immunol. 2006;43:86–96.
Eisen DP, Dean MM, Boermeester MA, Fidler KJ, Gordon AC, Kronborg G, Kun JF, Lau YL, Payeras A, Valdimarsson H, Brett SJ, Ip WK, Mila J, Peters MJ, Saevarsdottir S, van Till JW, Hinds CJ, McBryde ES. Low serum mannose-binding lectin level increases the risk of death due to pneumococcal infection. Clin Infect Dis. 2008;47:510–6.
Lee SJ, Gonzalez-Aseguinolaza G, Nussenzweig MC. Disseminated candidiasis and hepatic malarial infection in mannose-binding-lectin-A-deficient mice. Mol Cell Biol. 2002;22:8199–203.
Tan Y, Liu L, Luo P, Wang A, Jia T, Shen X, Wang M, Zhang S. Association between mannose-binding lectin and HIV infection and progression in a Chinese population. Mol Immunol. 2009;47:632–8.
Donders GG, Babula O, Bellen G, Linhares IM, Witkin SS. Mannose-binding lectin gene polymorphism and resistance to therapy in women with recurrent vulvovaginal candidiasis. BJOG. 2008;115:1225–31.
van Till JW, Modderman PW, de Boer M, Hart MH, Beld MG, Boermeester MA. Mannose-binding lectin deficiency facilitates abdominal Candida infections in patients with secondary peritonitis. Clin Vaccine Immunol. 2008;15:65–70.
Mikulska M, Calandra T, Sanguinetti M, Poulain D, Viscoli C. The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia. Crit Care. 2010;14:R222.
Jouault T, Sarazin A, Martinez-Esparza M, Fradin C, Sendid B, Poulain D. Host responses to a versatile commensal: PAMPs and PRRs interplay leading to tolerance or infection by Candida albicans. Cell Microbiol. 2009;11:1007–15.
van de Veerdonk FL, Marijnissen RJ, Kullberg BJ, Koenen HJ, Cheng SC, Joosten I, van den Berg WB, Williams DL, van der Meer JW, Joosten LA, Netea MG. The macrophage mannose receptor induces IL-17 in response to Candida albicans. Cell Host Microbe. 2009;5:329–40.
Fradin C, Poulain D, Jouault T. beta-1,2-linked oligomannosides from Candida albicans bind to a 32-kilodalton macrophage membrane protein homologous to the mammalian lectin galectin-3. Infect Immun. 2000;68:4391–8.
Gil ML, Gozalbo D. TLR2, but not TLR4, triggers cytokine production by murine cells in response to Candida albicans yeasts and hyphae. Microbes Infect. 2006;8:2299–304.
Netea MG, Van Der Graaf CA, Vonk AG, Verschueren I, Van Der Meer JW, Kullberg BJ. The role of toll-like receptor (TLR) 2 and TLR4 in the host defense against disseminated candidiasis. J Infect Dis. 2002;185:1483–9.
Jouault T, Ibata-Ombetta S, Takeuchi O, Trinel PA, Sacchetti P, Lefebvre P, Akira S, Poulain D. Candida albicans phospholipomannan is sensed through toll-like receptors. J Infect Dis. 2003;188:165–72.
Cambi A, Beeren I, Joosten B, Fransen JA, Figdor CG. The C-type lectin DC-SIGN internalizes soluble antigens and HIV-1 virions via a clathrin-dependent mechanism. Eur J Immunol. 2009;39:1923–8.
Ma YJ, Doni A, Hummelshoj T, Honore C, Bastone A, Mantovani A, Thielens NM, Garred P. Synergy between ficolin-2 and pentraxin 3 boosts innate immune recognition and complement deposition. J Biol Chem. 2009;284:28263–75.
Brummer E, Stevens DA. Collectins and fungal pathogens: roles of surfactant proteins and mannose binding lectin in host resistance. Med Mycol. 2010;48:16–28.
Takahashi M, Iwaki D, Kanno K, Ishida Y, Xiong J, Matsushita M, Endo Y, Miura S, Ishii N, Sugamura K, Fujita T. Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 contributes to activation of the lectin complement pathway. J Immunol. 2008;180:6132–8.
Liu F, Liao Q, Liu Z. Mannose-binding lectin and vulvovaginal candidiasis. Int J Gynaecol Obstet. 2006;92:43–7.
Lillegard JB, Sim RB, Thorkildson P, Gates MA, Kozel TR. Recognition of Candida albicans by mannan-binding lectin in vitro and in vivo. J Infect Dis. 2006;193:1589–97.
Acknowledgements
This work was supported by a grant from the “Programme Hospitalier de Recherche Clinique du Ministère des Affaires Sociales, de la Santé et de la Ville.″ PHRC 1918, 2011-10-27, by INSERM, and by the European Community’s Seventh Framework Program (FP7-2007-2013) under grant agreement no. HEALTH-F2-2010-260338 ‘ALLFUN’. We thank Dr Val Hopwood for editing the manuscript.
Transparency Declaration
All authors have no commercial relationship or conflict of interest of any nature related to the present study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Damiens, S., Poissy, J., François, N. et al. Mannose-Binding Lectin Levels and Variation During Invasive Candidiasis. J Clin Immunol 32, 1317–1323 (2012). https://doi.org/10.1007/s10875-012-9748-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10875-012-9748-2