Chicken CD14, unlike mammalian CD14, is trans-membrane rather than GPI-anchored

Z, Wu; Rothwell, Lisa; Hu, Tuanjun; Kaiser, Pete

doi:10.1016/j.dci.2008.07.008

Cited by 34 publications

(26 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The outcome of TLR response is also dependent on the cell-type. Recently, it has become possible to isolate and culture chicken dendritic cells (Hansell et al 2007;Wu et al 2009), and the availability of markers should enable better isolation and characterization into subgroups of these cells. It will be important to identify which TLRs these sub-populations express and how they respond to TLR activation; this should help to clarify the role of TLRs in linking innate with adaptive immunity in avian species.…”

Section: Discussionmentioning

confidence: 99%

“…Mammalian CD14 is expressed as a GPI-anchored cell surface protein (mCD14) which can be released as a soluble serum protein (sCD14) by proteolytic cleavage or phospholipase-induced shedding (Schütt 1999); sCD14 confers LPS sensitivity to cells not expressing mCD14. However, chicken CD14 differs from mammalian CD14 in being a transmembrane protein with a small cytoplasmic tail of 25 amino acids (Wu et al 2009); thus, chickens may not produce sCD14 and this together with the absence of serum LPB may also account for the reduced sensitivity of chickens to LPS. Chicken CD14 RNA is expressed in most lymphoid and nonlymphoid tissues as is also reported for mammalian CD14 RNA (Wu et al 2009).…”

Section: Tlr4mentioning

confidence: 98%

“…However, chicken CD14 differs from mammalian CD14 in being a transmembrane protein with a small cytoplasmic tail of 25 amino acids (Wu et al 2009); thus, chickens may not produce sCD14 and this together with the absence of serum LPB may also account for the reduced sensitivity of chickens to LPS. Chicken CD14 RNA is expressed in most lymphoid and nonlymphoid tissues as is also reported for mammalian CD14 RNA (Wu et al 2009). …”

Section: Tlr4mentioning

confidence: 98%

“…Chicken CD14 shows 34% protein homology with human CD14 and shares several structural features such as conserved LRRs and conserved cysteines (Wu et al 2009), but its role in LPS recognition/presentation and recognition of other MAMPS remains to be defined. Mammalian CD14 is expressed as a GPI-anchored cell surface protein (mCD14) which can be released as a soluble serum protein (sCD14) by proteolytic cleavage or phospholipase-induced shedding (Schütt 1999); sCD14 confers LPS sensitivity to cells not expressing mCD14.…”

Section: Tlr4mentioning

confidence: 98%

“…However, only recently have the availability of markers allowed the isolation of DCs from chickens (Hansell et al 2007;Wu et al 2009), and as these cells play critical immunological roles (e.g., viral surveillance, antigen presentation, cross-priming), characterization of avian DC subpopulations and their expression of TLRs is essential to a better understanding of avian immunology.…”

Section: Tlr3 7 and 21mentioning

confidence: 99%

See 4 more Smart Citations

Avian toll-like receptors

2010

View full text Add to dashboard Cite

Analysis of the genomes of two distantly related bird species, chicken and zebra finch (divergence of about 100 million years), indicate that there are ten avian toll-like receptors and that five of these, TLR2a, 2b, 3, 4, 5 and 7, are clear orthologs to TLRs found in mammals. Duplication of genes has led to TLR1La and 1Lb, TLR2a and 2b, and two TLR7s in the zebra finch. Avian TLR21 may be orthologous to TLR21 found in fish and amphibians, and avian TLR15, which is phylogenetically related to the TLR2 family, appears to be unique to avian species. While TLR2 is conserved between mammalian and avian species, the other TLR2 family members evolved independently. Dimerization between either of the two avian TLR2 species and TLR1La or 1Lb permits recognition of the same broad range of molecules as recognized by mammalian TLR2 dimerized with either TLR1, 6 and 10. Similarly, while TLR9 has been lost from the avian genome, DNA high in unmethylated CpG motifs is immunostimulatory through avian TLR21 which is absent in mammals. Thus, while some TLR members were commonly retained in both mammals and birds, others were separately lost or gained, or diverged independently; but broadly speaking the TLRs of the two classes of vertebrates evolved to recognize very similar spectra of microbial products. Components of downstream TLR signaling are also mostly conserved but with some losses in avian species; notably, TRAM is absent in avian genomes and, hence, the TRIF/TRAM-dependent signaling pathway utilized by mammals in LPS activation appears to be absent in birds.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Tlr4mentioning

confidence: 98%

Section: Tlr4mentioning

confidence: 98%

Section: Tlr4mentioning

confidence: 98%

Section: Tlr3 7 and 21mentioning

confidence: 99%

See 3 more Smart Citations

Avian toll-like receptors

2010

View full text Add to dashboard Cite

show abstract

Tracing the evolution of novel features of human Toll‐like receptor 4

et al. 2019

View full text Add to dashboard Cite

Toll-like receptor 4 (TLR4) is a critical innate immune protein that activates inflammation in response to extracellular cues. Much of the work to understand how the protein works in humans has been done using mouse models. Although human and mouse TLR4 have many shared features, they have also diverged significantly since their last common ancestor, acquiring 277 sequence differences. Functional differences include the extent of ligand-independent activation, whether lipid IVa acts as an antagonist or agonist, and the relative species cross-compatibility of their MD-2 cofactor. We set out to understand the evolutionary origins for these functional differences between human and mouse TLR4. Using a combination of phylogenetics, ancestral sequence reconstruction, and functional characterization, we found that evolutionary changes to the human TLR4, rather than changes to the mouse TLR4, were largely responsible for these functional changes. Human TLR4 repressed ancestral ligand-independent activity and gained antagonism to lipid IVa. Additionally, mutations to the human TLR4 cofactor MD-2 led to lineage-specific incompatibility between human and opossum TLR4 complex members. These results were surprising, as mouse TLR4 has acquired many more mutations than human TLR4 since their last common ancestor. Our work has polarized this set of transitions and sets up work to study the mechanistic underpinnings for the evolution of new functions in TLR4.Additional Supporting Information may be found in the online version of this article. Jeremy A. Anderson and Andrea N. Loes contributed equally to this work. Significance statement:We used an evolutionary lens to compare human and mouse innate immune proteins. We found several ways that both the human and mouse proteins have changed significantly since their last common ancestor. This provides context for interpreting studies in mice to understand human biology and health.

show abstract

Avian Antigen-Presenting Cells

Kaspers

Kaiser

2014

Avian Immunology

View full text Add to dashboard Cite

Chicken CD14, unlike mammalian CD14, is trans-membrane rather than GPI-anchored

Cited by 34 publications

References 38 publications

Avian toll-like receptors

Avian toll-like receptors

Tracing the evolution of novel features of human Toll‐like receptor 4

Avian Antigen-Presenting Cells

Contact Info

Product

Resources

About