Transmembrane Oligomeric form of Vibrio cholerae Cytolysin Triggers TLR2/TLR6-dependent Pro-inflammatory Responses in Monocytes and Macrophages

Vibrio cholerae cytolysin (VCC) kills target eukaryotic cells by forming transmembrane oligomeric β-barrel pores. Once irreversibly converted into the transmembrane oligomeric form, VCC acquires unusual structural stability, and loses cytotoxic property. It is therefore possible that upon exerting its cytotoxic activity, oligomeric form of VCC retained in the disintegrated membrane fractions of the lysed cells would survive within the host cellular milieu for sufficiently prolonged duration, without causing any further cytotoxicity. Under such circumstances, VCC oligomers may potentially be recognized by the host immune cells. Based on such hypothesis, in the present study we have explored the interaction of the transmembrane oligomeric form of VCC with the monocytes and macrophage cells of the innate immune system. Our study shows that the VCC oligomers assembled in the liposome membranes elicit potent pro-inflammatory responses in the monocytes and macrophages, via stimulation of the TLR2/TLR6-dependent signalling cascades that involve MyD88/IRAK1/TRAF6. VCC oligomer-mediated pro-inflammatory responses critically depend on the activation of the transcription factor NF-kB. Pro-inflammatory responses induced by the VCC oligomers also require activation of the MAPK family member JNK, which presumably acts via stimulation of the transcription factor AP-1. Notably, role of the MAPK p38 could not be documented in the process.

Source: BJ Signal - November 28, 2014 Category: Biochemistry Authors: B Khilwani, A Mukhopadhaya, K Chattopadhyay Tags: BJ Signal Source Type: research