Mycopathologia

, Volume 167, Issue 4, pp 173–180 | Cite as

Mannose-Binding Lectin Serum Levels are Low in Persons with Clinically Active Coccidioidomycosis

  • Neil M. Ampel
  • Sara O. Dionne
  • Andrea Giblin
  • Abigail B. Podany
  • John Galgiani
Article

Abstract

Background

Mannose-binding lectin (MBL) is a circulating collectin that is part of the innate immune response. We explored the serum levels of MBL in persons with different forms of coccidioidomycosis.

Methods

Serum MBL was measured by ELISA from samples obtained from healthy donors with immunity to Coccidioides, and those with various forms of active coccidioidomycosis. Blood cell specimens from a subgroup of subjects with active coccidioidomycosis were examined for single nucleotide polymorphisms of the MBL gene and promoter regions.

Results

The control group comprised 29 healthy immune subjects. Patient groups with active coccidioidomycosis consisted of 20 patients with symptomatic primary pulmonary coccidioidomycosis, 26 with non-meningeal disseminated coccidioidomycosis, and nine with coccidioidal meningitis. The group with active coccidioidomycosis was significantly older and more likely to be male than the control group (for both, P < 0.001). The mean ± SEM level of serum MBL in the healthy controls was 169.4 ± 28.6 ng/ml, significantly higher than the 79.2 ± 10.9 ng/ml for all active groups (P < 0.001). Moreover, the active coccidioidomycosis group was significantly more likely to have serum MBL level ≤70 ng/ml compared to the control group (P = 0.001). Genetic analysis in 27 subjects with active coccidioidomycosis revealed marked variation based on race and ethnicity. Among a subgroup of 10 white, non-hispanic men with active coccidioidomycosis, there was a significant association between the H and P haplotypes and MBL levels ≤70 ng/ml (P < 0.036 and P < 0.035, respectively).

Conclusions

These data suggest that there is an association between low serum MBL levels and symptomatic coccidioidomycosis.

Keywords

Coccidioidomycosis Coccidioides Mannose binding lectin Innate immunity Collectins Human 

References

  1. 1.
    Garred P, Larsen F, Seyfarth J, Fujita R, Madsen HO. Mannose-binding lectin and its genetic variants. Genes Immun. 2006;7(2):85–94. doi:10.1038/sj.gene.6364283.PubMedCrossRefGoogle Scholar
  2. 2.
    Bouwman LH, Roep BO, Roos A. Mannose-binding lectin: clinical implications for infection, transplantation, and autoimmunity. Hum Immunol. 2006;67(4–5):247–56. doi:10.1016/j.humimm.2006.02.030.PubMedCrossRefGoogle Scholar
  3. 3.
    Super M, Thiel S, Lu J, Levinsky RJ, Turner MW. Association of low levels of mannan-binding protein with a common defect of opsonisation. Lancet. 1989;334(8674):1236–9. doi:10.1016/S0140-6736(89)91849-7.CrossRefGoogle Scholar
  4. 4.
    Eisen DP, Minchinton RM. Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin Infect Dis. 2003;37(11):1496–505. doi:10.1086/379324.PubMedCrossRefGoogle Scholar
  5. 5.
    Luty AJ, Kun JF, Kremsner PG. Mannose-binding lectin plasma levels and gene polymorphisms in Plasmodium falciparum malaria. J Infect Dis. 1998;178(4):1221–4. doi:10.1086/515690.PubMedCrossRefGoogle Scholar
  6. 6.
    Kirkpatrick BD, Huston CD, Wagner D, Noel F, Rouzier P, Pape JW, et al. Serum mannose-binding lectin deficiency is associated with cryptosporidiosis in young Haitian children. Clin Infect Dis. 2006;43(3):289–94. doi:10.1086/505396.PubMedCrossRefGoogle Scholar
  7. 7.
    Pappagianis D. Epidemiology of coccidioidomycosis. Curr Top Med Mycol. 1988;2:199–238.PubMedGoogle Scholar
  8. 8.
    Fisher MC, Koenig GL, White TJ, Taylor JW. Molecular and phenotypic description of Coccidioides posadasii sp. nov., previously recognized as the non-California population of Coccidioides immitis. Mycologia. 2002;94(1):73–84. doi:10.2307/3761847.CrossRefGoogle Scholar
  9. 9.
    Pappagianis D, Putman EW, Kobayashi GS. Polysaccharide of Coccidioides immitis. J Bact. 1961;82:714–23.PubMedGoogle Scholar
  10. 10.
    Ampel NM, Nelson DK, Li L, Dionne SO, Lake DF, Simmons KA, et al. The mannose receptor mediates the cellular immune response in human coccidioidomycosis. Infect Immun. 2005;73(4):2554–5. doi:10.1128/IAI.73.4.2554-2555.2005.PubMedCrossRefGoogle Scholar
  11. 11.
    Dionne SO, Podany AB, Ruiz YW, Ampel NM, Galgiani JN, Lake DF. Spherules derived from Coccidioides posadasii promote human dendritic cell maturation and activation. Infect Immun. 2006;74(4):2415–22. doi:10.1128/IAI.74.4.2415-2422.2006.PubMedCrossRefGoogle Scholar
  12. 12.
    Burgess JL, Fierro MA, Lantz RC, Hysong TA, Fleming JE, Gerkin R, et al. Longitudinal decline in lung function: evaluation of interleukin-10 genetic polymorphisms in firefighters. J Occup Environ Med. 2004;46(10):1013–22. doi:10.1097/01.jom.0000141668.70006.52.PubMedCrossRefGoogle Scholar
  13. 13.
    Eder W, Klimecki W, Yu L, von Mutius E, Riedler J, Braun-Fahrlander C, et al. Toll-like receptor 2 as a major gene for asthma in children of European farmers. J Allergy Clin Immunol. 2004;113(3):482–8. doi:10.1016/j.jaci.2003.12.374.PubMedCrossRefGoogle Scholar
  14. 14.
    Eisen DP, Stubbs J, Spilsbury D, Carnie J, Leydon J, Howden BP. Low mannose-binding lectin complement activation function is associated with predisposition to Legionnaires’ disease. Clin Exp Immunol. 2007;149(1):97–102.PubMedGoogle Scholar
  15. 15.
    Thiel S, Holmskov U, Hviid L, Laursen SB, Jensenius JC. The concentration of the C-type lectin, mannan-binding protein, in human plasma increases during an acute phase response. Clin Exp Immunol. 1992;90(1):31–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Rantala A, Lajunen T, Juvonen R, Bloigu A, Silvennoinen-Kassinen S, Peitso A, et al. Mannose-binding lectin concentrations, MBL2 polymorphisms, and susceptibility to respiratory tract infections in young men. J Infect Dis. 2008;198(8):1247–53. doi:10.1086/591912.PubMedCrossRefGoogle Scholar
  17. 17.
    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(6):630–41. doi:10.1046/j.1365-3083.2002.01167.x.PubMedCrossRefGoogle Scholar
  18. 18.
    Giraldo PC, Babula O, Goncalves AK, Linhares IM, Amaral RL, Ledger WJ, et al. Mannose-binding lectin gene polymorphism, vulvovaginal candidiasis, and bacterial vaginosis. Obstet Gynecol. 2007;109(5):1123–8.PubMedGoogle Scholar
  19. 19.
    Vaid M, Kaur S, Sambatakou H, Madan T, Denning DW, Sarma PU. Distinct alleles of mannose-binding lectin (MBL) and surfactant proteins A (SP-A) in patients with chronic cavitary pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Clin Chem Lab Med. 2007;45(2):183–6. doi:10.1515/CCLM.2007.033.PubMedCrossRefGoogle Scholar
  20. 20.
    Kaur S, Gupta VK, Thiel S, Sarma PU, Madan T. Protective role of mannan-binding lectin in a murine model of invasive pulmonary aspergillosis. Clin Exp Immunol. 2007;148(2):382–9. doi:10.1111/j.1365-2249.2007.03351.x.PubMedCrossRefGoogle Scholar
  21. 21.
    Eisen DP, Dean MM, O’Sullivan MV, Heatley S, Minchinton RM. Mannose-binding lectin deficiency does not appear to predispose to cryptococcosis in non-immunocompromised patients. Med Mycol. 2008;46(4):371–5. doi:10.1080/13693780701874515.PubMedCrossRefGoogle Scholar
  22. 22.
    Cox RA, Pope RM, Stevens DA. Immune complexes in coccidioidomycosis. Correlation with disease involvement. Am Rev Respir Dis. 1982;126(3):439–43.PubMedGoogle Scholar
  23. 23.
    Turner MW. The role of mannose-binding lectin in health and disease. Mol Immunol. 2003;40(7):423–9. doi:10.1016/S0161-5890(03)00155-X.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Neil M. Ampel
    • 1
  • Sara O. Dionne
    • 1
  • Andrea Giblin
    • 1
  • Abigail B. Podany
    • 1
  • John Galgiani
    • 1
  1. 1.The Valley Fever Center for Excellence, Medical Service (1-111)The University of Arizona College of Medicine, and the Southern Arizona Veterans Affairs Health Care SystemTucsonUSA

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