title: Hemolysin induces Toll-like receptor (TLR)-independent apoptosis and multiple TLR-associated parallel activation of macrophages.
abstract: Vibrio cholerae hemolysin (HlyA) displays bipartite property while supervising macrophages (MΦ). The pore-forming toxin causes profound apoptosis within 3 h of exposure and in parallel supports activation of the defying MΦ. HlyA-induced apoptosis of MΦ remains steady for 24 h, is Toll-like receptor (TLR)-independent, and is driven by caspase-9 and caspase-7, thus involving the mitochondrial or intrinsic pathway. Cell activation is carried forward by time dependent up-regulation of varying TLRs. The promiscuous TLR association of HlyA prompted investigation, which revealed the β-prism lectin domain of HlyA simulated TLR4 up-regulation by jacalin, a plant lectin homologue besides expressing CD86 and type I cytokines TNF-α and IL-12. However, HlyA cytolytic protein domain up-regulated TLR2, which controlled CD40 for continuity of cell activation. Expression of TOLLIP before TLR2 and TLR6 abrogated TLR4, CD40, and CD86. We show that the transient expression of TOLLIP leading to curbing of activation-associated capabilities is a plausible feedback mechanism of MΦ to deploy TLR2 and prolong activation involving CD40 to encounter the HlyA cytolysin domain.
authors.affiliation: Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata 700 010, India.
authors.forename: Deep Chandan
authors.initials: DC
authors.lastname: Chakraborty
authors.forename: Gayatri
authors.initials: G
authors.lastname: Mukherjee
authors.forename: Pallavi
authors.initials: P
authors.lastname: Banerjee
authors.forename: Kalyan K
authors.initials: KK
authors.lastname: Banerjee
authors.forename: Tapas
authors.initials: T
authors.lastname: Biswas
mesh_terms: D000818:Animals; D017209:Apoptosis; D051940:B7-2 Antigen / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000378:metabolism*; D019013:CD40 Antigens / Q000096:biosynthesis; D053179:Caspase 7 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D006460:Hemolysin Proteins / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051216:Toll-Like Receptor 6 / Q000378:metabolism*
chemical_list: D051940:B7-2 Antigen; D001426:Bacterial Proteins; D019013:CD40 Antigens; D006460:Hemolysin Proteins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; C084287:hlyA protein, Vibrio cholerae; D053179:Caspase 7; D053453:Caspase 9