Legionella pp 541-551

Part of the Methods in Molecular Biology book series (MIMB, volume 954)

Human Susceptibility to Legionnaires’ Disease



Legionella pneumophila is a facultative intracellular pathogen that is an important cause of pneumonia. Although host factors that may predispose to acquisition of Legionnaire’s Disease (LD) include comorbid illnesses (e.g., diabetes, chronic lung disease), age, male sex, and smoking, many individuals have no identifiable risk factors. Some studies suggest that genetic factors may enhance susceptibility to LD. In this chapter we discuss current techniques and scientific methods to identify genetic susceptibility factors. These genetic studies provide insight into the human immune response to intracellular pathogens and may improve strategies for treatment and vaccine development.

Key words

Legionella pneumophila Macrophage Single-nucleotide polymorphisms 


  1. 1.
    Dominguez A, Alvarez J, Sabria M et al (2009) Factors influencing the case-fatality rate of Legionnaires’ disease. Int J Tuberc Lung Dis 13:407–412PubMedGoogle Scholar
  2. 2.
    Edelstein PH, Meyer RD (1984) Legionnaires’ disease. A review. Chest 85:114–120PubMedCrossRefGoogle Scholar
  3. 3.
    Hawn TR, Verbon A, Janer M et al (2005) Toll-like receptor 4 polymorphisms are associated with resistance to Legionnaires’ disease. Proc Natl Acad Sci USA 102:2487–2489PubMedCrossRefGoogle Scholar
  4. 4.
    Hawn TR, Verbon A, Lettinga KD et al (2003) A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires’ disease. J Exp Med 198:1563–1572PubMedCrossRefGoogle Scholar
  5. 5.
    Kruglyak L, Nickerson DA (2001) Variation is the spice of life. Nat Genet 27:234–236PubMedCrossRefGoogle Scholar
  6. 6.
    Casanova JL, Abel L (2002) Genetic dissection of immunity to mycobacteria: the human model. Annu Rev Immunol 20:581–620PubMedCrossRefGoogle Scholar
  7. 7.
    Gasser RB, Hu M, Chilton NB et al (2006) Single-strand conformation polymorphism (SSCP) for the analysis of genetic variation. Nat Protoc 1:3121–3128PubMedCrossRefGoogle Scholar
  8. 8.
    Stanssens P, Zabeau M, Meersseman G et al (2004) High-throughput MALDI-TOF discovery of genomic sequence polymorphisms. Genome Res 14:126–133PubMedCrossRefGoogle Scholar
  9. 9.
    Lee LG, Connell CR, Bloch W (1993) Allelic discrimination by nick-translation PCR with fluorogenic probes. Nucleic Acids Res 21:3761–3766PubMedCrossRefGoogle Scholar
  10. 10.
    Sebat J, Lakshmi B, Malhotra D et al (2007) Strong association of de novo copy number mutations with autism. Science 316:445–449PubMedCrossRefGoogle Scholar
  11. 11.
    Diskin SJ, Hou C, Glessner JT et al (2009) Copy number variation at 1q21.1 associated with neuroblastoma. Nature 459:987–991PubMedCrossRefGoogle Scholar
  12. 12.
    Johnson CM, Lyle EA, Omueti KO et al (2007) Cutting edge: A common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy. J Immunol 178:7520–7524PubMedGoogle Scholar
  13. 13.
    Gregory SG, Schmidt S, Seth P et al (2007) Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat Genet 39:1083–1091PubMedCrossRefGoogle Scholar
  14. 14.
    Nackley AG, Shabalina SA, Tchivileva IE et al (2006) Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science 314:1930–1933PubMedCrossRefGoogle Scholar
  15. 15.
    Kimchi-Sarfaty C, Oh JM, Kim IW et al (2007) A “silent” polymorphism in the MDR1 gene changes substrate specificity. Science 315:525–528PubMedCrossRefGoogle Scholar
  16. 16.
    Brest P, Lapaquette P, Souidi M et al (2011) A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn’s disease. Nat Genet 43:242–245PubMedCrossRefGoogle Scholar
  17. 17.
    Knight JC, Udalova I, Hill AV et al (1999) A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria. Nat Genet 22:145–150PubMedCrossRefGoogle Scholar
  18. 18.
    Clop A, Marcq F, Takeda H et al (2006) A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nat Genet 38:813–818PubMedCrossRefGoogle Scholar
  19. 19.
    Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Statist Soc Ser B 57:289–300Google Scholar
  20. 20.
    Storey JD (2002) A direct approach to false discovery rates. J Roy Statist Soc Ser B 64:479–498CrossRefGoogle Scholar
  21. 21.
    Gao X (2011) Multiple testing corrections for imputed SNPs. Genet Epidemiol 35:154–158PubMedCrossRefGoogle Scholar
  22. 22.
    Johnson RC, Nelson GW, Troyer JL et al (2010) Accounting for multiple comparisons in a genome-wide association study (GWAS). BMC Genomics 11:724PubMedCrossRefGoogle Scholar
  23. 23.
    Berrington WR, Macdonald M, Khadge S et al (2010) Common polymorphisms in the NOD2 gene region are associated with leprosy and its reactive states. J Infect Dis 201:1422–1435PubMedCrossRefGoogle Scholar
  24. 24.
    Spielman RS, McGinnis RE, Ewens WJ (1993) Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 52:506–516PubMedGoogle Scholar
  25. 25.
    Barreiro LB, Neyrolles O, Babb CL et al (2006) Promoter variation in the DC-SIGN-encoding gene CD209 is associated with tuberculosis. PLoS Med 3:e20PubMedCrossRefGoogle Scholar
  26. 26.
    Price AL, Patterson NJ, Plenge RM et al (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38:904–909PubMedCrossRefGoogle Scholar
  27. 27.
    Jallow M, Teo YY, Small KS et al (2009) Genome-wide and fine-resolution association analysis of malaria in West Africa. Nat Genet 41:657–665PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Division of Allergy and Infectious Diseases, Department of MedicineUniversity of Washington School of MedicineSeattleUSA

Personalised recommendations