Tuesday, September 19, 2017

TLR4 / TLR8, cd16, and NK cells

Just supporting the notion that TLR8 is the TLR of the ER for viral infections there

Nk cells with FcR(cd16)  will make IFNgamma and TNF
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2188858/

TLR8 and cd16
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148764

Hepatitis C : flavivirus and Hepatitis B : polyomavirus

Hepatitis B(a polyomavirus which infects the ER then nucleus) and Nk
https://www.ncbi.nlm.nih.gov/pubmed/20643584

Hepatitis C (a flavivirus that like yellow fever looks like it infects the ER)
https://www.ncbi.nlm.nih.gov/pubmed/16571411

Hep C infects the ER
https://www.ncbi.nlm.nih.gov/pubmed/15817385

Yellow fever and the ER
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC525104/

Yellow fever and Hep C I had previously suggested used the melanocortin 4 receptor which looks like it takes them to the ER

TLR 7 is the nucleus and TLR 8 is the ER

Hepatitis B with TLR7/8
https://www.ncbi.nlm.nih.gov/pubmed/26315138

Hepatits C with tlr7/8.
https://www.ncbi.nlm.nih.gov/pubmed/28122964

The KIR (cd158) is the HLA receptor on NK cells
http://journal.frontiersin.org/article/10.3389/fimmu.2014.00105/full

KIR has the strongest affinity for HLA-C because when the polyomavirus infects the ER very little HLA-C makes it to the surface and these are the infected cells NK needs to destroy

TLR8 might be the weakest because many polyomaviruses inhibit the production of TLRs and HLAs from inside the endoplasmic reticulum. This absence of TLR or HLA-C could be how killer T cells evolved  to automatically kill "naked cells" and why killer T cells secrete IFN gamma.

polyomavirus tumors and NK
http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000924

So how does TLR4 trigger the NK ?

TLR4 binds lipopolysaccharides on gram neg bacteria (like e.coli)

TLR4 and cd16
http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000464

E.coli  binds CD16 and tries to block
https://www.ncbi.nlm.nih.gov/pubmed/17934470
http://onlinelibrary.wiley.com/store/10.1002/eji.201546118/asset/eji3678.pdf?v=1&t=j7s0btvu&s=e6ad34a57c13f6f3e475ffe1fe5862f5ac4e9883

NK are also triggered by aggregated antibodies

CD16 binds the aggregated IgG or complexed IgG
https://ximbio.com/reagent/151919/anti-cd16-3g8

AXL/gas6 and the il-15 pathway for NK
http://www.bloodjournal.org/content/bloodjournal/113/11/2470.full.pdf?sso-checked=true

il-15 is a cytokine made by macrophages and dendritic cells following viral infection

TNF alpha stimulates the secretion of il-15
https://www.ncbi.nlm.nih.gov/pubmed/23950892

TNF alpha is released by the macrophage/dendritic cell that is infected or when Nk are activated by cd16

TNF alpha and NK
https://www.ncbi.nlm.nih.gov/pubmed/8207246





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