Beta defensin

β-defensins are coding for genes which impact the function of the innate immune system.[3] These genes are responsible for production of antimicrobial peptides found in white blood cells such as macrophages, granulocytes and NK-cells, β-defensins are also found in epithelial cells.[4] Single-nucleotide polymorphisms (SNPs) are found in genes coding for β-defensins.[5] The presences of SNPs are lower in the coding regions compared to non-coding regions.[5] The appearance of SNPs in the coding region will highly likely affecting the resistance against infections through changes in the protein sequences which will give rise to different biological functions.[5]

Receptors such as toll-like receptors (TLR) and nod-like receptors (NLR) will activate the immune system by binding of ligands such as lipopolysaccharides and peptidoglycan.[6] Toll-like receptors are expressed in intestinal epithelial cells [7] or antigen presenting cells (APCs) such as dendritic cells, B-lymphocytes and macrophages.[6] When the receptors are activated a cascade reaction will take place and substances such as cytokines and antimicrobial peptides[8] will be released.[6]

β-defensins are cationic and can therefore interact with the membrane of invading microbes, which are negative due to lipopolysaccharides (LPS) and lipoteichoic acid (LTA) found in the cell membrane.[1] The peptides have higher affinity to the binding site compared to Ca2+ and Mg2+ ions.[5] The peptides will therefore exchange place with those ions, thus affecting the stability of the membrane.[5] The peptides have a greater size compared with the ions which cause changes in the membrane structure.[5] Due to changes in the electric potential, peptides will pass across the membrane and thus aggregate into dimers.[9] Pore complex will be created as a result of breaking the hydrogen bonds between the amino acids in the terminal end of the strands connecting defensins monomers.[9] Formation of pore complex will cause membrane depolarization and cell lysis.[5]

Defensins not only have the ability to strengthen the innate immune system but can also enhance the adaptive immune system by chemotaxis of monocytes, T-lymphocytes, dendritic cells and mast cells to the infection site.[5] Defensins will also improve the capacity of macrophage phagocytosis.[5]

β-defensins are classified in three classes and Avian β-defensins constitute for one of the classes.[3] This division is based on Zhang's classification and both the length, the homology of the peptides and the gene structure are factors affecting the classification.[9]

Avian β-defensins are separated in avian heterophiles and non-heterophiles. Avian heterophiles can be divided into two sub-classes, depending on the number of present homologous residues in the genome.[9]

Avian heterophiles lack protective oxidative mechanisms, such as superoxide and myeloperoxidase. Making non-oxidative mechanisms, such as lysosomes and cationic peptides, even more important.[9]

β-defensins genes are found across the vertebrates, including mammals, reptiles, birds and fish.[10] The fact that alpha and theta defensins are absence in older vertebrates, like birds and fishes, indicates that defensins must have evolved from the same ancestral gene coding for β-defensins.[11] Indeed, these defensins of this superfamily are related to the 'big defensins' which are found in invertebrate animals, indicating even earlier origins.[10]

In 2001, it was thought that β-defensins were similar to the ancestral defensin from a comparison of sequences of β-defensins, α-defensins and insect defensins.[12] Subsequent structural analyses have suggested that the β-defensins, α-defensins, θ-defensins and big defensins share an evolutionary origin, but are separate to the defensins found in insects, fungi and plants.[13]

In addition to other antimicrobial defensins, there are related defensin-like proteins with have evolved other functions. These include toxins found in snakes (e.g. crotamine), bearded lizards and platypus.[14]

The first beta-defensin discovered was Tracheal Antimicrobial Peptide, found in the bovine airway in 1991.[15] The first human beta-defensin, HBD1, was discovered in 1995,[2] followed by the HBD2 in 1997.[16]

DEFB1; DEFB103A; DEFB105A; DEFB105B; DEFB106; DEFB108B; DEFB109; DEFB110; DEFB111; DEFB114; DEFB130; DEFB136; DEFB4; SPAG11A;

• Defensin
  • α-defensin
  • β-defensin
  • θ-defensin
• Lingual antimicrobial peptide