The quorum sensing volatile molecule 2-amino acetophenon modulates host immune responses in a manner that promotes life with unwanted guests.

Autor: Arunava Bandyopadhaya, Meenu Kesarwani, Yok-Ai Que, Jianxin He, Katie Padfield, Ronald Tompkins, Laurence G Rahme
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: PLoS Pathogens, Vol 8, Iss 11, p e1003024 (2012)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1003024
Popis: Increasing evidence indicates that bacterial quorum sensing (QS) signals are important mediators of immunomodulation. However, whether microbes utilize these immunomodulatory signals to maintain infection remain unclear. Here, we show that the Pseudomonas aeruginosa QS-regulated molecule 2-amino acetophenone (2-AA) modulates host immune responses in a manner that increases host ability to cope with this pathogen. Mice treated with 2-AA prior to infection had a 90% survival compared to 10% survival rate observed in the non-pretreated infected mice. Whilst 2-AA stimulation activates key innate immune response pathways involving mitogen-activated protein kinases (MAPKs), nuclear factor (NF)-κB, and pro-inflammatory cytokines, it attenuates immune response activation upon pretreatment, most likely by upregulating anti-inflammatory cytokines. 2-AA host pretreatment is characterized by a transcriptionally regulated block of c-JUN N-terminal kinase (JNK) and NF-κB activation, with relatively preserved activation of extracellular regulated kinase (ERK) 1/2. These kinase changes lead to CCAAT/enhancer-binding protein-β (c/EBPβ) activation and formation of the c/EBPβ-p65 complex that prevents NF-κB activation. 2-AA's aptitude for dampening the inflammatory processes while increasing host survival and pathogen persistence concurs with its ability to signal bacteria to switch to a chronic infection mode. Our results reveal a QS immunomodulatory signal that promotes original aspects of interkingdom communication. We propose that this communication facilitates pathogen persistence, while enabling host tolerance to infection.
Databáze: Directory of Open Access Journals
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