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Basement membrane and cell integrity of self-tissues in maintaining Drosophila immunological tolerance.

Kim MJ, Choe KM - PLoS Genet. (2014)

Bottom Line: We found that the basement membrane endows otherwise susceptible target tissues with self-tolerance that prevents autoimmunity, and further demonstrated that laminin is a key component for both structural maintenance and the self-tolerance checkpoint function of the basement membrane.Moreover, we found that cell integrity, as determined by cell-cell interaction and apicobasal polarity, functions as a second discrete checkpoint.Target tissues became vulnerable to blood cell encapsulation and subsequent melanization only after loss of both the basement membrane and cell integrity.

View Article: PubMed Central - PubMed

Affiliation: Department of Systems Biology, Yonsei University, Seodaemun-gu, Seoul, South Korea.

ABSTRACT
The mechanism underlying immune system recognition of different types of pathogens has been extensively studied over the past few decades; however, the mechanism by which healthy self-tissue evades an attack by its own immune system is less well-understood. Here, we established an autoimmune model of melanotic mass formation in Drosophila by genetically disrupting the basement membrane. We found that the basement membrane endows otherwise susceptible target tissues with self-tolerance that prevents autoimmunity, and further demonstrated that laminin is a key component for both structural maintenance and the self-tolerance checkpoint function of the basement membrane. Moreover, we found that cell integrity, as determined by cell-cell interaction and apicobasal polarity, functions as a second discrete checkpoint. Target tissues became vulnerable to blood cell encapsulation and subsequent melanization only after loss of both the basement membrane and cell integrity.

No MeSH data available.


Related in: MedlinePlus

Proposed model for the self-tolerance checkpoint function in the Drosophila immune system.Epithelial tissues are equipped with at least two self-tolerance checkpoints: BM laminin and cell integrity. The latter is currently less well-defined but appears to include apicobasal cell polarity and cell-cell adhesion. With either one of the checkpoints, self-tissue may become tolerant to the immune system of its own. Upon Mmp2 overexpression (OE), the salivary gland loses BM integrity to an extent that allows plasmatocyte access; however, cell integrity remains largely intact (intact 2nd checkpoint). Upon integrin knockdown (KD) in the salivary gland (AB1>mys-i), cells lose cell integrity, while the organ maintains the BM (intact 1st checkpoint). In the presence of laminin knockdown, both of the self-tolerance checkpoints are non-functional, and the tissues are subjected to lamellocyte encapsulation. Avirulent parasitoid eggs or wing disc implants from distantly related species [11] do not have either of the checkpoints that are compatible with the host immune system, and thus, these foreign bodies are also sequestered by lamellocyte encapsulation.
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pgen-1004683-g006: Proposed model for the self-tolerance checkpoint function in the Drosophila immune system.Epithelial tissues are equipped with at least two self-tolerance checkpoints: BM laminin and cell integrity. The latter is currently less well-defined but appears to include apicobasal cell polarity and cell-cell adhesion. With either one of the checkpoints, self-tissue may become tolerant to the immune system of its own. Upon Mmp2 overexpression (OE), the salivary gland loses BM integrity to an extent that allows plasmatocyte access; however, cell integrity remains largely intact (intact 2nd checkpoint). Upon integrin knockdown (KD) in the salivary gland (AB1>mys-i), cells lose cell integrity, while the organ maintains the BM (intact 1st checkpoint). In the presence of laminin knockdown, both of the self-tolerance checkpoints are non-functional, and the tissues are subjected to lamellocyte encapsulation. Avirulent parasitoid eggs or wing disc implants from distantly related species [11] do not have either of the checkpoints that are compatible with the host immune system, and thus, these foreign bodies are also sequestered by lamellocyte encapsulation.

Mentions: Based on the results of these studies, we propose that BM laminin on target tissues functions as a crucial component not only in BM assembly but as a tolerance checkpoint to self-tissues (Figure 6). As a self-tolerance checkpoint, the BM may either serve as a physical barrier or provide an inhibitory ligand for hemocyte receptors. We speculate that the latter is the case for several reasons. First, the heterospecific implantation experiments described above suggest that the hemocyte recognizes the BM structure of its own species [11]. Second, insect hemocytes are known to encapsulate a wide range of foreign materials, from parasitoid wasp eggs to synthetic beads, when injected into the hemocoel [37], [43], [44]. Encapsulation of parasites is faster than encapsulation of non-parasitic, heterospecific implants [discussed in 11]. Thus, hemocytes must be equipped with various cell surface receptors, including some as activating receptors with different binding spectra for pathogen-associated molecular patterns, and others as inhibitory receptors with narrow binding specificities to self-tissues. More specifically, laminin-coating of Sephadex beads inhibit melanotic encapsulation of the beads in mosquito hemocoel [43]. The outer surface of the Plasmodium oocyst appears to bind to mosquito-derived laminin upon passage through the midgut epithelium of the mosquito [45], suggesting that the insect laminin may indeed serve as an inhibitory ligand to hemocytes of its own species.


Basement membrane and cell integrity of self-tissues in maintaining Drosophila immunological tolerance.

Kim MJ, Choe KM - PLoS Genet. (2014)

Proposed model for the self-tolerance checkpoint function in the Drosophila immune system.Epithelial tissues are equipped with at least two self-tolerance checkpoints: BM laminin and cell integrity. The latter is currently less well-defined but appears to include apicobasal cell polarity and cell-cell adhesion. With either one of the checkpoints, self-tissue may become tolerant to the immune system of its own. Upon Mmp2 overexpression (OE), the salivary gland loses BM integrity to an extent that allows plasmatocyte access; however, cell integrity remains largely intact (intact 2nd checkpoint). Upon integrin knockdown (KD) in the salivary gland (AB1>mys-i), cells lose cell integrity, while the organ maintains the BM (intact 1st checkpoint). In the presence of laminin knockdown, both of the self-tolerance checkpoints are non-functional, and the tissues are subjected to lamellocyte encapsulation. Avirulent parasitoid eggs or wing disc implants from distantly related species [11] do not have either of the checkpoints that are compatible with the host immune system, and thus, these foreign bodies are also sequestered by lamellocyte encapsulation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199487&req=5

pgen-1004683-g006: Proposed model for the self-tolerance checkpoint function in the Drosophila immune system.Epithelial tissues are equipped with at least two self-tolerance checkpoints: BM laminin and cell integrity. The latter is currently less well-defined but appears to include apicobasal cell polarity and cell-cell adhesion. With either one of the checkpoints, self-tissue may become tolerant to the immune system of its own. Upon Mmp2 overexpression (OE), the salivary gland loses BM integrity to an extent that allows plasmatocyte access; however, cell integrity remains largely intact (intact 2nd checkpoint). Upon integrin knockdown (KD) in the salivary gland (AB1>mys-i), cells lose cell integrity, while the organ maintains the BM (intact 1st checkpoint). In the presence of laminin knockdown, both of the self-tolerance checkpoints are non-functional, and the tissues are subjected to lamellocyte encapsulation. Avirulent parasitoid eggs or wing disc implants from distantly related species [11] do not have either of the checkpoints that are compatible with the host immune system, and thus, these foreign bodies are also sequestered by lamellocyte encapsulation.
Mentions: Based on the results of these studies, we propose that BM laminin on target tissues functions as a crucial component not only in BM assembly but as a tolerance checkpoint to self-tissues (Figure 6). As a self-tolerance checkpoint, the BM may either serve as a physical barrier or provide an inhibitory ligand for hemocyte receptors. We speculate that the latter is the case for several reasons. First, the heterospecific implantation experiments described above suggest that the hemocyte recognizes the BM structure of its own species [11]. Second, insect hemocytes are known to encapsulate a wide range of foreign materials, from parasitoid wasp eggs to synthetic beads, when injected into the hemocoel [37], [43], [44]. Encapsulation of parasites is faster than encapsulation of non-parasitic, heterospecific implants [discussed in 11]. Thus, hemocytes must be equipped with various cell surface receptors, including some as activating receptors with different binding spectra for pathogen-associated molecular patterns, and others as inhibitory receptors with narrow binding specificities to self-tissues. More specifically, laminin-coating of Sephadex beads inhibit melanotic encapsulation of the beads in mosquito hemocoel [43]. The outer surface of the Plasmodium oocyst appears to bind to mosquito-derived laminin upon passage through the midgut epithelium of the mosquito [45], suggesting that the insect laminin may indeed serve as an inhibitory ligand to hemocytes of its own species.

Bottom Line: We found that the basement membrane endows otherwise susceptible target tissues with self-tolerance that prevents autoimmunity, and further demonstrated that laminin is a key component for both structural maintenance and the self-tolerance checkpoint function of the basement membrane.Moreover, we found that cell integrity, as determined by cell-cell interaction and apicobasal polarity, functions as a second discrete checkpoint.Target tissues became vulnerable to blood cell encapsulation and subsequent melanization only after loss of both the basement membrane and cell integrity.

View Article: PubMed Central - PubMed

Affiliation: Department of Systems Biology, Yonsei University, Seodaemun-gu, Seoul, South Korea.

ABSTRACT
The mechanism underlying immune system recognition of different types of pathogens has been extensively studied over the past few decades; however, the mechanism by which healthy self-tissue evades an attack by its own immune system is less well-understood. Here, we established an autoimmune model of melanotic mass formation in Drosophila by genetically disrupting the basement membrane. We found that the basement membrane endows otherwise susceptible target tissues with self-tolerance that prevents autoimmunity, and further demonstrated that laminin is a key component for both structural maintenance and the self-tolerance checkpoint function of the basement membrane. Moreover, we found that cell integrity, as determined by cell-cell interaction and apicobasal polarity, functions as a second discrete checkpoint. Target tissues became vulnerable to blood cell encapsulation and subsequent melanization only after loss of both the basement membrane and cell integrity.

No MeSH data available.


Related in: MedlinePlus