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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

Predicted domain organization of NAIP proteins from different species. Red oval, BIR domain; blue rectangle, NACHT domain; lilac diamonds, LRR domain. Domain information derived from Ting et al. [57] and Romanish et al. [58].
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RSOB120015F3: Predicted domain organization of NAIP proteins from different species. Red oval, BIR domain; blue rectangle, NACHT domain; lilac diamonds, LRR domain. Domain information derived from Ting et al. [57] and Romanish et al. [58].

Mentions: The NLRC4:NAIP inflammasome provides an intriguing tale of species-specific behaviour in PRR biology. NLRC4 is a member of the NLR family that possesses an N-terminal CARD effector domain and forms an inflammasome complex that activates caspase 1 in response to stimulation with flagellin or type III secretion system proteins such as PrgJ from Salmonella [55,56]. Recently, the NAIP (also known as NLRB and Birc1; figure 3) proteins have been identified as a second group of NLR proteins involved in the formation of the NLRC4 inflammasome. It had been known for a while that murine NAIP5 was important for the control of, and immune response to, flagellin from Legionella pneumophila [59–61]. Subsequently, the groups of Vance and Shao have shown that different murine NAIP proteins provide the molecular basis for detection of specific ligands and signal through the formation of an inflammasome in conjunction with NLRC4 [62,63]. Specifically, murine NAIP2 is required for the detection of type III secretion components, while either murine NAIP5 or murine NAIP6 are capable of responding to flagellin. As yet the ligands, should there be any, detected by the remaining four mice NAIP proteins have not been identified. Murine NAIP3 and NAIP4 are reported to contain only baculoviral inhibition of apoptosis protein repeat (BIR) domains [57] and therefore may have a regulatory role, rather than one involved in detection.Figure 3.


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

Bryant CE, Monie TP - Open Biol (2012)

Predicted domain organization of NAIP proteins from different species. Red oval, BIR domain; blue rectangle, NACHT domain; lilac diamonds, LRR domain. Domain information derived from Ting et al. [57] and Romanish et al. [58].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

RSOB120015F3: Predicted domain organization of NAIP proteins from different species. Red oval, BIR domain; blue rectangle, NACHT domain; lilac diamonds, LRR domain. Domain information derived from Ting et al. [57] and Romanish et al. [58].
Mentions: The NLRC4:NAIP inflammasome provides an intriguing tale of species-specific behaviour in PRR biology. NLRC4 is a member of the NLR family that possesses an N-terminal CARD effector domain and forms an inflammasome complex that activates caspase 1 in response to stimulation with flagellin or type III secretion system proteins such as PrgJ from Salmonella [55,56]. Recently, the NAIP (also known as NLRB and Birc1; figure 3) proteins have been identified as a second group of NLR proteins involved in the formation of the NLRC4 inflammasome. It had been known for a while that murine NAIP5 was important for the control of, and immune response to, flagellin from Legionella pneumophila [59–61]. Subsequently, the groups of Vance and Shao have shown that different murine NAIP proteins provide the molecular basis for detection of specific ligands and signal through the formation of an inflammasome in conjunction with NLRC4 [62,63]. Specifically, murine NAIP2 is required for the detection of type III secretion components, while either murine NAIP5 or murine NAIP6 are capable of responding to flagellin. As yet the ligands, should there be any, detected by the remaining four mice NAIP proteins have not been identified. Murine NAIP3 and NAIP4 are reported to contain only baculoviral inhibition of apoptosis protein repeat (BIR) domains [57] and therefore may have a regulatory role, rather than one involved in detection.Figure 3.

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