Skip to main content
Article thumbnail
Location of Repository

Toll-like receptors (TLRs) and mannan-binding lectin (MBL): On constant alert in a hostile environment

By Ingrid-Maria Bergman


In the beginning were neither B cells nor T cells nor antibodies, but innate immune defense alone. The primary functional theme of innate immunity is the distinction between self and non-self, which is maintained by a vast number of cellular and subcellular components. In this context, the immense importance of the Toll-like receptors (TLRs) is well established. Positive (Darwinian) selection seems to be acting on the ligand-binding domains of these molecules, suggesting a selection pattern similar to that previously observed in the MHC proteins. In sharp contrast to TLRs, the biological significance of mannan-binding lectin (MBL) is controversial, and, concerning humans, it has been suggested that low concentration of MBL in serum represents a selective advantage. In this mini-review, based on a doctoral thesis, evolutionary aspects of TLRs and MBL are discussed

Topics: Review Article
Publisher: Informa Healthcare
OAI identifier:
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles


    1. (2008). A conserved Toll-like receptor is required for Caenorhabditis elegans innate immunity. EMBO Rep.
    2. (1997). A human homologue of the Drosophila Toll protein signals activation of adaptive immunity.
    3. A novel mannose-binding lectin/ ficolin-associated protein is highly expressed in heart and skeletal muscle tissues and inhibits complement activation.
    4. Adaptation and constraint at Tolllike receptors in primates.
    5. Biased distribution of single nucleotide polymorphisms (SNPs) in porcine Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR5, and TLR6 genes.
    6. Cloning and characterization of mannose-binding lectin from lamprey (Agnathans).
    7. (2008). Combinational recognition of bacterial lipoproteins and peptidoglycan by chicken Toll-like receptor 2 subfamily. Dev Comp Immunol.
    8. Comparative genetics and innate immune functions of collagenous lectins in animals. Vet ImmunolImmunopathol.
    9. (2008). Comparative study of the human ficolins reveals unique features of
    10. Complement and immune defense: from innate immunity to human diseases.
    11. (2009). Complement: coming full circle. Arch ImmunolTherExp (Warsz).
    12. (2007). Conserved and distinct aspects of the avian Toll-like receptor (TLR) system: implications for transmission and control of bird-borne zoonoses.BiochemSoc Trans.
    13. Crosstalk pathways between Toll-like receptors and the complement system. Trends Immunol.
    14. Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide.
    15. Decoding the patterns of self and nonself by the innate immune system.
    16. Deviation from major codons in the Toll-like receptor genes is associated with low Toll-like receptor expression.
    17. (2003). Direct binding of Toll-like receptor 2 to zymosan, and zymosan-induced NF-kappa B activation and TNF-alpha secretion are down-regulated by lung collectin surfactant protein
    18. Discrimination between host and pathogens by the complement system.
    19. Domain architecture evolution of pattern-recognition receptors.
    20. Edfors I. European wild boars and domestic pigs display different polymorphic patterns in the Toll-like receptor (TLR) 1, TLR2, and TLR6 genes.
    21. (2006). etal.Evolutionaryinsightsintothehighworldwideprevalenceof MBL2 deficiency alleles. Hum Mol Genet.
    22. (2008). Evasion of innate immune responses: evidence for mannose binding lectin inhibition of tumor necrosis factor alpha production by macrophages in response to Blastomyces dermatitidis. Infect Immun.
    23. Evidence for positive selection in the TLR9 gene of teleosts.
    24. Evolution and diversity of fish genomes.
    25. (2002). Evolution of the TIR, Tolls and TLRs: functional inferences from computational biology. Curr Top MicrobiolImmunol.
    26. (2009). Evolutionary dynamics of human Toll-like receptors and their different contributions to host defense. PLoS Genet.
    27. FCN1, FCN2 and FCN3-the genes behind the initiation of the lectin pathway of complement.
    28. From evolutionary genetics to human immunology: how selection shapes host defence genes. Nat Rev Genet.
    29. Functional characterization of full-length TLR3, IRAK-4, and TRAF6 in zebrafish (Daniorerio).
    30. GarlandaC,MainaV,CotenaA,MoalliaF.Thesolublepattern recognitionreceptorpentraxin-3ininnateimmunity,inflammation and fertility.
    31. Gene conversion limits divergence of mammalian TLR1 and TLR6.
    32. Genetic analysis of the innate immune responses in wild-derived inbred strains of mice.
    33. (2008). Genomic analysis of the immune gene repertoire of amphioxus reveals extraordinary innate complexity and diversity. Genome Res.
    34. Haplotype variation in bovine Toll-like receptor 4 and computational prediction of a positively selected ligand-binding domain.
    35. Higher intensity of purifying selection on >90% of the human genes revealed by the intrinsic replacement mutation rates.
    36. HughesAL,PiontkivskaH.Functionaldiversificationofthetolllike receptor gene family.
    37. Human and non-human primate genomes share hotspots of positive selection. PLoS Genet. 2010;6:e1000840. TLRs and MBL: On constant alert in a hostile environment 99
    38. Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88.
    39. Identification and characterization of porcine mannan-binding lectin A (pMBL-A), and determination of serum concentration heritability.
    40. (2004). Innate immunity in plants and animals: striking similarities and obvious differences. Immunol Rev.
    41. Innate immunity of fish (overview).
    42. Innate immunity-cross-talk with adaptive immunity through pattern recognition receptors and cytokines.
    43. Lamprey TLRs with properties distinct from those of the variable lymphocyte receptors.
    44. Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level.
    45. Manipulation of innate immunity by bacterial pathogens.
    46. (2001). Mannan-binding lectin enhances susceptibility to visceral leishmaniasis. Infect Immun.
    47. Mannan-binding lectin in the sub-Saharan HIV and tuberculosis epidemics.
    48. (2006). Mannose-binding lectin and its genetic variants. Genes Immun.
    49. Mannose-binding lectin and susceptibility to tuberculosis: a meta-analysis.
    50. Molecular cloning and characterisation of two homologues of Mannose-Binding TLRs and MBL: On constant alert in a hostile environment 97Lectin in rainbow trout.
    51. Molecular evolution of bovine Toll-like receptor 2 suggests substitutions of functional relevance.
    52. MusikacharoenT,YoshikaiY.Cuttingedge:naturallyoccurring soluble form of mouse Toll-like receptor 4 inhibits lipopolysaccharide signaling.
    53. (2005). Negative regulation of toll-like receptor-mediated immune responses. Nat Rev Immunol.
    54. Nonlinear dynamics of nonsynonymous (dN) and synonymous (dS) substitution rates affects inference of selection.
    55. (2008). O’Neill AJO. Signalling of Toll-like receptors.
    56. Pattern recognition receptors and control of adaptive immunity.
    57. Phylogenetic and expression analysis of amphibian Xenopus Toll-like receptors.
    58. Phylogenetic aspects of the complement system.
    59. Polymorphism distribution and structural conservation in RNA-sensing Toll-like receptors 3, 7, and 8 in pigs.
    60. (2008). Porcine Toll-like receptors: the front line of pathogen monitoring and possible implications for disease resistance. Dev Comp Immunol.
    61. Regulation of Toll-like receptor-mediated inflammatory response by complement in vivo.
    62. Sensing bacterial flagellin by membrane and soluble orthologs of Toll-like receptor 5 in rainbow trout (Onchorhynchusmikiss).
    63. (2004). Sequence analysis of the mannose-binding lectin (MBL2) gene reveals a high degree of heterozygosity with evidence of selection. Genes Immun.
    64. (2004). Serum lectin with known structure activates complement through the classical pathway.
    65. (2007). Siglecs and their roles in the immune system. Nat Rev Immunol.
    66. Signal regulatory proteins in the immune system.
    67. Small mannose-binding lectin-associated protein plays a regulatory role in the lectin complement pathway.
    68. Soluble forms of Toll-like receptor (TLR)2 capable of modulating TLR2 signaling are present in human plasma and breast milk.
    69. Structural insight into the mechanism of activation of the Toll receptor by the dimeric ligand Spätzle.
    70. (2005). The ‘involution’ of mannose-binding lectin. Hum Mol Genet.
    71. The evolution of vertebrate Toll-like receptors.
    72. (2007). The functions of plant TIR domains. SciSTKE.
    73. (2006). The immune gene repertoire encoded in the purple sea urchin genome. Dev Biol.
    74. (2008). The population genetics of dN/dS. PLoS Genet.
    75. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol.
    76. (2006). Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis.
    77. Toll-like receptor signaling in bony fish.
    78. (2001). Toll-like receptors and innate immunity. Nat Rev Immunol.
    79. (2007). Toll-like receptors in brain development and homeostasis.
    80. Toll-like receptors in innate immunity.
    81. (2010). Toll-like receptors: very clever molecules. Available at:
    82. TurnerMW.The roleofmannose-binding lectininhealthand disease.
    83. (2009). Variation matters: TLR structure and species-specific pathogen recognition. Trends Immunol.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.