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Mice, men and the relatives: cross-species studies underpin innate immunity.

Bryant CE, Monie TP - Open Biol (2012)

Bottom Line: Information obtained from Drospohila melanogaster, knock-out and knock-in mice, and through the use of forward genetics has resulted in discoveries that have opened our eyes to the functionality and complexity of the innate immune system.With the current increase in genomic information, the range of innate immune receptors and pathways of other species available to study is rapidly increasing, and provides a rich resource to continue the development of innate immune research.Here, we address some of the highlights of cross-species study in the innate immune field and consider the benefits of widening the species-field further.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.

ABSTRACT
The innate immune response is the first line of defence against infection. Germ-line-encoded receptors recognize conserved molecular motifs from both exogenous and endogenous sources. Receptor activation results in the initiation of a pro-inflammatory immune response that enables the resolution of infection. Understanding the inner workings of the innate immune system is a fundamental requirement in the search to understand the basis of health and disease. The development of new vaccinations, the treatment of pathogenic infection, the generation of therapies for chronic and auto-inflammatory disorders, and the ongoing battle against cancer, diabetes and atherosclerosis will all benefit from a greater understanding of innate immunity. The rate of knowledge acquisition in this area has been outstanding. It has been underpinned and driven by the use of model organisms. Information obtained from Drospohila melanogaster, knock-out and knock-in mice, and through the use of forward genetics has resulted in discoveries that have opened our eyes to the functionality and complexity of the innate immune system. With the current increase in genomic information, the range of innate immune receptors and pathways of other species available to study is rapidly increasing, and provides a rich resource to continue the development of innate immune research. Here, we address some of the highlights of cross-species study in the innate immune field and consider the benefits of widening the species-field further.

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Related in: MedlinePlus

Murine and human TLR ectodomain structures are nearly identical. (a) Overlay of the ectodomains of murine TLR3 (PDB 3ciy, red) and both human TLR3 structures (PDB 2a0z, orange; PDB 1ziw, blue). (b) Overlay of the human (PDB 2z63, blue) and murine (PDB 2z64, red) ectodomains of TLR4. Structures are shown in a ribbon representation. Images were generated using the PyMOL molecular graphics system, v. 1.3, Schrödinger, LLC.
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RSOB120015F2: Murine and human TLR ectodomain structures are nearly identical. (a) Overlay of the ectodomains of murine TLR3 (PDB 3ciy, red) and both human TLR3 structures (PDB 2a0z, orange; PDB 1ziw, blue). (b) Overlay of the human (PDB 2z63, blue) and murine (PDB 2z64, red) ectodomains of TLR4. Structures are shown in a ribbon representation. Images were generated using the PyMOL molecular graphics system, v. 1.3, Schrödinger, LLC.

Mentions: Solving the structures of murine, in addition to human PRRs is particularly enticing for two main reasons. First, a large proportion of PRR functional work is performed in murine cells. Second, the sequence identity between murine and human proteins is sufficient for the resultant structures to be highly similar. Consequently, they provide an excellent framework for understanding the molecular basis of receptor function in the absence of human information. This is highlighted by the structural similarities between the murine and human receptors of TLR3 and TLR4 (figure 2 and table 2). In fact, the TLR3 structures are so similar that the observed root mean square deviation of either of the solved human apo-TLR3 structures with the murine ligand-bound structure [39] is comparable to that between the two human structures (table 2).Table 2.


Mice, men and the relatives: cross-species studies underpin innate immunity.

Bryant CE, Monie TP - Open Biol (2012)

Murine and human TLR ectodomain structures are nearly identical. (a) Overlay of the ectodomains of murine TLR3 (PDB 3ciy, red) and both human TLR3 structures (PDB 2a0z, orange; PDB 1ziw, blue). (b) Overlay of the human (PDB 2z63, blue) and murine (PDB 2z64, red) ectodomains of TLR4. Structures are shown in a ribbon representation. Images were generated using the PyMOL molecular graphics system, v. 1.3, Schrödinger, LLC.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376732&req=5

RSOB120015F2: Murine and human TLR ectodomain structures are nearly identical. (a) Overlay of the ectodomains of murine TLR3 (PDB 3ciy, red) and both human TLR3 structures (PDB 2a0z, orange; PDB 1ziw, blue). (b) Overlay of the human (PDB 2z63, blue) and murine (PDB 2z64, red) ectodomains of TLR4. Structures are shown in a ribbon representation. Images were generated using the PyMOL molecular graphics system, v. 1.3, Schrödinger, LLC.
Mentions: Solving the structures of murine, in addition to human PRRs is particularly enticing for two main reasons. First, a large proportion of PRR functional work is performed in murine cells. Second, the sequence identity between murine and human proteins is sufficient for the resultant structures to be highly similar. Consequently, they provide an excellent framework for understanding the molecular basis of receptor function in the absence of human information. This is highlighted by the structural similarities between the murine and human receptors of TLR3 and TLR4 (figure 2 and table 2). In fact, the TLR3 structures are so similar that the observed root mean square deviation of either of the solved human apo-TLR3 structures with the murine ligand-bound structure [39] is comparable to that between the two human structures (table 2).Table 2.

Bottom Line: Information obtained from Drospohila melanogaster, knock-out and knock-in mice, and through the use of forward genetics has resulted in discoveries that have opened our eyes to the functionality and complexity of the innate immune system.With the current increase in genomic information, the range of innate immune receptors and pathways of other species available to study is rapidly increasing, and provides a rich resource to continue the development of innate immune research.Here, we address some of the highlights of cross-species study in the innate immune field and consider the benefits of widening the species-field further.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.

ABSTRACT
The innate immune response is the first line of defence against infection. Germ-line-encoded receptors recognize conserved molecular motifs from both exogenous and endogenous sources. Receptor activation results in the initiation of a pro-inflammatory immune response that enables the resolution of infection. Understanding the inner workings of the innate immune system is a fundamental requirement in the search to understand the basis of health and disease. The development of new vaccinations, the treatment of pathogenic infection, the generation of therapies for chronic and auto-inflammatory disorders, and the ongoing battle against cancer, diabetes and atherosclerosis will all benefit from a greater understanding of innate immunity. The rate of knowledge acquisition in this area has been outstanding. It has been underpinned and driven by the use of model organisms. Information obtained from Drospohila melanogaster, knock-out and knock-in mice, and through the use of forward genetics has resulted in discoveries that have opened our eyes to the functionality and complexity of the innate immune system. With the current increase in genomic information, the range of innate immune receptors and pathways of other species available to study is rapidly increasing, and provides a rich resource to continue the development of innate immune research. Here, we address some of the highlights of cross-species study in the innate immune field and consider the benefits of widening the species-field further.

Show MeSH
Related in: MedlinePlus