The quorum sensing volatile molecule 2-amino acetophenon modulates host immune responses in a manner that promotes life with unwanted guests
Authors: Yok-Ai Que
Arunava Bandyopadhaya
Laurence G Rahme
Jianxin He
Meenu Kesarwani
Katie Padfield
Ronald Tompkins
Journal: PLoS Pathogens (2012)
Discipline: MICROBIOLOGY
Keywords: bacterial quorum sensing; immunomodulation; Pseudomonas aeruginosa; 2-amino acetophenone; host immune responses
Affiliations: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America.

Abstract:  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. 

Retracted: No

PubPeer comments:
 Figure 6 and Figure 8: * Red boxes arrows show unexpected similarities between the  no Pre actin blots in figure 6A and 6B, the 2-AA Pre actin blot in Figure 6C, and the actin blot in Figure 8B. In the latter case, the orientation , vertical stretch, and experiment appears to be different from that in Figure 6. ![file] ![file] , 
 Figure 7B appears to also have a couple of the lanes of the blot shown in red in the previous comment. ![file] , 
 Dear Elizabeth, Thank you so much for your comments. In Figure 6 the same actin control was used in Fig 6 since the same filter was used with the different antibodies. However, looking at the Fig. 6 again, we realized that the actin control of Fig 6c are switched between No Pre and 2AA Pre . We will request correction. Regarding Fig 7b, the incorrect actin control is in Fig 8B instead, which we will also correct. Please let us know if this is clear. Thank you so much again for bringing this to our attention. Laurence and Arunava ,