Toll-Like Receptor Evolution: Does Temperature Matter?

Abstract

Toll-like receptors (TLRs) recognize conserved pathogen-associated molecular patterns (PAMPs) and are an ancient and well-conserved group of pattern recognition receptors (PRRs). The isolation of the Antarctic continent and its unique teleost fish and microbiota prompted the present investigation into Tlr evolution. Gene homologues of tlr members in teleosts from temperate regions were present in the genome of Antarctic Nototheniidae and the non-Antarctic sister lineage Bovichtidae. Overall, in Nototheniidae apart from D. mawsoni, no major tlr gene family expansion or contraction occurred. Instead, lineage and species-specific changes in the ectodomain and LRR of Tlrs occurred, particularly in the Tlr11 superfamily that is well represented in fish. Positive selective pressure and associated sequence modifications in the TLR ectodomain and within the leucine-rich repeats (LRR), important for pathogen recognition, occurred in Tlr5, Tlr8, Tlr13, Tlr21, Tlr22, and Tlr23 presumably associated with the unique Antarctic microbiota. Exposure to lipopolysaccharide (Escherichia coli O111:B4) Gram negative bacteria did not modify tlr gene expression in N. rossii head–kidney or anterior intestine, although increased water temperature (+4°C) had a significant effect.

Transcriptomic Down-Regulation of Immune System Components in Barrier and Hematopoietic Tissues after Lipopolysaccharide Injection in Antarctic Notothenia coriiceps

“…The PRR response to LPS in N. coriiceps diverged from the more commonly described TLR in other teleost fish [122] and instead NLR and MRC receptor genes were more responsive. The lack of TLR response could be linked to the recent observation that TLR5, TLR8, TLR21, TLR22 and TLR23 are under positive selective pressure in Antarctic Notothenioids [41]. Furthermore, a study of deep-sea bacteria revealed pathogen associated molecular patterns (PAMPs) that failed to interact with human TLR, and this was explained by the absence of selective pressure for their recognition during pathogen-recognition receptors (PRR) evolution and so they were "immune silent" [123].…”

“…The lysozyme and antiprotease activities in blood plasma were measured based on previously described methods [56,57] with modifications [41]. Lyophilized Micrococcus luteus cells, hen egg white lysozyme, trypsin from porcine pancreas, azocasein and buffers were purchased from Sigma-Aldrich.…”

“…In the bullhead (Notothenia coriiceps), damage repair of skin occurred at a slower pace than in teleosts from warmer waters with no sign of contamination by pathogens, which was attributed to the protective action of the mucous layer or the low pathogenicity of microorganism in Antarctic seawater [39]. Studies taking a candidate gene approach revealed that the exposure of N. coriiceps and N. rossii to bacterial infection agonist lipopolysaccharide (LPS) modified toll-like receptor gene expression in liver, kidney and spleen [40,41] and modulated iron-related immune genes, including hepcidin 4 (hp4) [42]. A novel hepcidin (hepcidin type II) has been identified in the Antarctic Notothenioids Dissostichus mawsoni and Notothenia angustata and was shown to be under positive selection [43].…”

“…Liver of Antarctic bullhead exposed to heat killed bacteria or polyinosinic:polycytidylic acid (poly I:C) was enriched in antigen processing and presentation and bacterial ligand exposure transcripts, which use antigen presentation against bacterial infection, but it may also use other defense mechanisms, such as TNF-mediated apoptosis, against viral infection [44]. Several toll-like receptor genes within the Notothenioid clade were shown to be under positive selection in pathogen recognition domains suggesting adaptation to the specific Antarctic microbiota [41]. A proteome study of the head kidney between white blood fish, Chionodraco hamatus, and two red blood fish, Trematomus bernacchii and N. coriiceps, revealed differences in erythropoiesis, heme biogenesis, leucocyte, and platelet development, with upregulation of lymphoid and megakaryocytic lineage marker proteins in ice fish [45].…”

Role of TLRs in HIV-1 Infection and Potential of TLR Agonists in HIV-1 Vaccine Development and Treatment Strategies

“…They are classified as type I transmembrane receptors with a ligand-binding extracellular N-terminal domain, transmembrane region, and cytosolic signalling C-terminal domain ( Figure 2 ). The extracellular region of TLRs contains leucine-rich repeat (LRR) motifs which recognise PAMPs and DAMPs [ 32 ]. The LRR motif is found in many proteins that participate in immune recognition in plants and animals.…”