Hypothesis:
Parasitic cell death through inflammasome which create GSDM pores are not just to release il-1Beta but a 10-20 nm window revealing a piece of the parasite which also sticks to GSDM for IgE antibody binding triggering Eosinophils .
3 types of inflammasomes (wiki)
NLRP1 which forms when lethal toxins detected
NLRP3 which forms when PAMPS whole pathogens or microbial toxins are detected
IPAF which forms when flagellins are detected
The inflammasomes are active caspase-1 which cleave and create GSDM. Groups of which form the pores at the cells plasma membrane.
GSDM also binds cardolipin on parasites/mycobacteria/gram positive bacteria which would cause them to plug up the GSDM pore.
Cell Death
https://www.nature.com/articles/cr2017133/figures/1
inflammasome and GSDMD creates a pore in the plasma membrane
https://www.ncbi.nlm.nih.gov/pubmed/27383986?dopt=Abstract
20nm pore GSDMD
http://emboj.embopress.org/content/35/16/1766.abstract
GSDMD is the mechanism of cell death
http://emboj.embopress.org/content/35/16/1766.abstract
magnesium moves TH1 to TH2
https://www.ncbi.nlm.nih.gov/pubmed/23816766
Antibodies in T.gondii infections
https://www.ncbi.nlm.nih.gov/pubmed/24864110
GSDMD has a strong link to asthma
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135378/
IgE airway inflammation asthma
https://www.ncbi.nlm.nih.gov/pubmed/17760568
cardiolipin antibodies and t.gondii
https://eujournal.org/index.php/esj/article/view/4213
cardiolipin and mycobacteria
https://www.ncbi.nlm.nih.gov/pubmed/23910993
GSDMD pore induced traps (pit)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5565696/
diabetes and chronic back pain
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510921/
GSDMD expressed in all tissue types
https://www.proteinatlas.org/ENSG00000104518-GSDMD/tissue
Why would your body have 4 types? are they matching up with the antibodies somehow?
IgE at the skin's IGF-1 with the GSDMA pore?
IgA , GH with GSDMB ?
IgG1, insulin with GSDMC ?
looking at the disulfide bridges
https://www.researchgate.net/figure/A-Immunoglobulin-domain-structures-of-human-IgG1-4-and-IgA1-2-Schematic-representations_fig1_273470442
Septic shock from staph followed by Berger Disease (IgA)
https://www.ncbi.nlm.nih.gov/pubmed/12671604
septic shock patients and high GSDMB expression
https://www.ncbi.nlm.nih.gov/pubmed/30321352
GSDMD with macrophages which are the sentinel all over
phagocytosis with GSDMD
http://jem.rupress.org/content/213/10/2113
Note that this fits with il-5 not just triggering differentiation of eosinophils but switching the dimer IgA to the monomer form with tends to come from bone marrow. (at the mucosal region)
so during a T gondii infection damaged epithelial cells would release il-33 which triggers TH2 to make il-5 and il-13. il-33 would trigger the trogocytosis of mhc with bacteria from the cytosol to basophils who would then show Th2.
Eosinophis would then use Fc antibody binding to phagocytosis infected cells which it would then internally destroy them. The IgA antibody would would bind through the GSDM pore on cells that had cytosolic receptors (nods) triggered by t. gondii.
Trogocytosis on mhc from mD to basophil
https://academic.oup.com/intimm/article/30/9/391/4946541
TSLP thymic stromal lymphopoietin creates the langerhans and converts th2 into Tfh.
What still needs to be elucidated is the relationship of the inflammasome with the GSDM pore. If the main purpose of the pore is to serve as a window to infections then the the virally triggered inflammasomes favor apoptosis not GSDM.
The AIM2 inflammasome appears to be connected to nuclear infections which would suggest that no GSDM pore would be formed since the infection is not in the cytosol. The NLRP3 inflammasomes on the other had seems to sway between apoptosis and pyroptosis.
AIM2 inflammasome and apoptosis, NLRP3 inflammasome and pyrotosis..and the fuzzy zone
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741496/
Viral infections tend to end with apoptosis while parasitic/bacterial infections need to end with pyroptosis.
extra cellular bacteria trigger tlrs to create ifn lambda
http://www.jimmunol.org/content/jimmunol/early/2017/09/27/jimmunol.1700250.full.pdf
ifn lambda from not just golgi viruses but from Bacteria in the cytosol
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328987/
Perhaps with different IFN triggered receptors (IFN Beta or IFN lambda) the NLRP3 inflammasome behaves differently?
IFNbeta receptors trigger caspase 8. FasL triggers caspase 8 too.
Parasitic cell death through inflammasome which create GSDM pores are not just to release il-1Beta but a 10-20 nm window revealing a piece of the parasite which also sticks to GSDM for IgE antibody binding triggering Eosinophils .
3 types of inflammasomes (wiki)
NLRP1 which forms when lethal toxins detected
NLRP3 which forms when PAMPS whole pathogens or microbial toxins are detected
IPAF which forms when flagellins are detected
The inflammasomes are active caspase-1 which cleave and create GSDM. Groups of which form the pores at the cells plasma membrane.
GSDM also binds cardolipin on parasites/mycobacteria/gram positive bacteria which would cause them to plug up the GSDM pore.
Cell Death
https://www.nature.com/articles/cr2017133/figures/1
inflammasome and GSDMD creates a pore in the plasma membrane
https://www.ncbi.nlm.nih.gov/pubmed/27383986?dopt=Abstract
20nm pore GSDMD
http://emboj.embopress.org/content/35/16/1766.abstract
GSDMD is the mechanism of cell death
http://emboj.embopress.org/content/35/16/1766.abstract
magnesium moves TH1 to TH2
https://www.ncbi.nlm.nih.gov/pubmed/23816766
Antibodies in T.gondii infections
https://www.ncbi.nlm.nih.gov/pubmed/24864110
GSDMD has a strong link to asthma
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135378/
IgE airway inflammation asthma
https://www.ncbi.nlm.nih.gov/pubmed/17760568
cardiolipin antibodies and t.gondii
https://eujournal.org/index.php/esj/article/view/4213
cardiolipin and mycobacteria
https://www.ncbi.nlm.nih.gov/pubmed/23910993
GSDMD pore induced traps (pit)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5565696/
diabetes and chronic back pain
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510921/
Hypothesis: using Human protein atlas : GSDM expression changes based on hormone
GSDMA IGF-1 of skin and umbilical cord
GSDMB growth hormone of the lungs and peyer patches (colon/intestine)
GSDMC has been linked to diabetes. The spleen grows into pancreas and it is in this area that insulin is high.
GSDMD expressed in all tissue types
https://www.proteinatlas.org/ENSG00000104518-GSDMD/tissue
Why would your body have 4 types? are they matching up with the antibodies somehow?
IgE at the skin's IGF-1 with the GSDMA pore?
IgA , GH with GSDMB ?
IgG1, insulin with GSDMC ?
looking at the disulfide bridges
https://www.researchgate.net/figure/A-Immunoglobulin-domain-structures-of-human-IgG1-4-and-IgA1-2-Schematic-representations_fig1_273470442
Septic shock from staph followed by Berger Disease (IgA)
https://www.ncbi.nlm.nih.gov/pubmed/12671604
septic shock patients and high GSDMB expression
https://www.ncbi.nlm.nih.gov/pubmed/30321352
GSDMD with macrophages which are the sentinel all over
phagocytosis with GSDMD
http://jem.rupress.org/content/213/10/2113
Note that this fits with il-5 not just triggering differentiation of eosinophils but switching the dimer IgA to the monomer form with tends to come from bone marrow. (at the mucosal region)
so during a T gondii infection damaged epithelial cells would release il-33 which triggers TH2 to make il-5 and il-13. il-33 would trigger the trogocytosis of mhc with bacteria from the cytosol to basophils who would then show Th2.
Eosinophis would then use Fc antibody binding to phagocytosis infected cells which it would then internally destroy them. The IgA antibody would would bind through the GSDM pore on cells that had cytosolic receptors (nods) triggered by t. gondii.
Trogocytosis on mhc from mD to basophil
https://academic.oup.com/intimm/article/30/9/391/4946541
TSLP thymic stromal lymphopoietin creates the langerhans and converts th2 into Tfh.
What still needs to be elucidated is the relationship of the inflammasome with the GSDM pore. If the main purpose of the pore is to serve as a window to infections then the the virally triggered inflammasomes favor apoptosis not GSDM.
The AIM2 inflammasome appears to be connected to nuclear infections which would suggest that no GSDM pore would be formed since the infection is not in the cytosol. The NLRP3 inflammasomes on the other had seems to sway between apoptosis and pyroptosis.
AIM2 inflammasome and apoptosis, NLRP3 inflammasome and pyrotosis..and the fuzzy zone
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741496/
Viral infections tend to end with apoptosis while parasitic/bacterial infections need to end with pyroptosis.
extra cellular bacteria trigger tlrs to create ifn lambda
http://www.jimmunol.org/content/jimmunol/early/2017/09/27/jimmunol.1700250.full.pdf
ifn lambda from not just golgi viruses but from Bacteria in the cytosol
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328987/
Perhaps with different IFN triggered receptors (IFN Beta or IFN lambda) the NLRP3 inflammasome behaves differently?
IFNbeta receptors trigger caspase 8. FasL triggers caspase 8 too.
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