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ESX5 associated PE proteins of Mycobacterium tuberculosis drives Th1 type polarization: an immunomodulatory paradigm
Mycobacterium tuberculosis (M.tb) harbors various effector molecules that affect human immune system. There exists a varied difference between the slow growing pathogenic mycobacteria compared to the fast growing non-pathogenic strains. One marked difference is the presence of ESX5, a type VII secre...
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Published in: | The Journal of immunology (1950) 2020-05, Vol.204 (1_Supplement), p.82-82.36 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | Mycobacterium tuberculosis (M.tb) harbors various effector molecules that affect human immune system. There exists a varied difference between the slow growing pathogenic mycobacteria compared to the fast growing non-pathogenic strains. One marked difference is the presence of ESX5, a type VII secretion system that is found to be most recently evolved and has been acquired by the pathogenic M.tb. ESX5 is involved in the secretion of an enigmatic PE/PPE family of proteins that are exclusive to the genus mycobacteriacea. PE/PPE are the effector virulent molecules that play vivid role in modulating host immune system. ESX5 locus has 2 pe genes and 3 ppe genes. Of the translated products, two PE proteins are paralogs, but contrastingly found to have different PPE binding partners as these proteins function as heterodimers, homodimers and individual proteins. THP1 macrophages (differentiated human monocytes) when treated with different micro-concentrations of PE 1X and PE 1Y induce differential Th1 type cytokine responses. PE 1X and PE 1Y induced stronger TNF-α response at 24hrs of protein exposure that increased markedly at 48hrs. IL-12 p70 was found to decrease from 24hrs to 48hrs during PE 1X treatment whereas PE 1Y exposure led to the secretion of IL-12 p70 which was constantly maintained from 24hrs to 48hrs of exposure time. PE 1X specifically mediated TLR2 dependent activation of macrophages that was responsible for the secretion of pro-inflammatory cytokines. On the contrary PE 1Y activated macrophages through TLR4 dependent cascade. These results therefore, conclude that PE 1X and PE 1Y contribute profoundly towards Th1 polarization of the immune response. |
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ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.204.Supp.82.36 |