On 2016 Mar 31, Damien Chaussabel commented:

I read your paper with great interest; this is excellent work with clear translational potential, so first of all congratulations on getting it published!

We are currently establishing a science education program that builds on the availability of large amounts of data in public repositories.

In this context we will encourage students/trainees to examine new noteworthy publications and to identify and share with the authors observations that may extend or build upon their original findings.

This is one of our first attempts! We hope that the exercise may also prove helpful to you:

A first observation is that in blood stimulated in vitro with a wide range of immune agonists, including pathogen-associated molecular patterns, heat-killed bacteria and cytokines, the patterns of induction of PKM2, IL6 and IL1B at the transcriptional level are rather distinct:

• IL1B shows high induction by Heat-killed E. coli (HK E. coli), Staph (HKSA) and Legionella (HKLP) as well as Flagellin, PAM3, R837, Zymosan, CpG; and some induction by LPS, RSV and TNF. http://www.interactivefigures.com:80/dm3/miniURL/view/L3 (just in case here is a 20 sec video showing how to view the data: https://youtu.be/MAtDFnLeeG0)

• IL6 shows high induction by Heat-killed E. coli (HK E. coli – which dominates the responses) and some induction by Heat-killed Staph (HKSA) and Legionella (HKLP), Flagellin, PAM3, Zymosan and CpG http://www.interactivefigures.com:80/dm3/miniURL/view/L4

• As for PKM2, first, induction levels are not as dramatic; second strikingly no response is seen following culture with HK E. coli. Compared to the “ex-vivo control” (=culture without stimulation); the most induction is seen with HKSA and HKLP, with possibly some induction seen with LPS, Flagellin, PAM3, Zymosan or TNF http://www.interactivefigures.com:80/dm3/miniURL/view/L2

The explanation might be trivial (at least to you!), but I found such disconnect puzzling, especially with regards to differences in levels of induction by HK E. coli.

Also, would you assume that the induction of PKM2 transcription correlates with dimerisation and nuclear translocation?

If that were the case would this phenomenon be driven by ROS released as a result of an innate response to bacteria from for instance neutrophils, independent of a change in the cellular glucose metabolism?

Thanks!

On 2016 Mar 31, Damien Chaussabel commented:

I read your paper with great interest; this is excellent work with clear translational potential, so first of all congratulations on getting it published!

We are currently establishing a science education program that builds on the availability of large amounts of data in public repositories.

In this context we will encourage students/trainees to examine new noteworthy publications and to identify and share with the authors observations that may extend or build upon their original findings.

This is one of our first attempts! We hope that the exercise may also prove helpful to you:

A first observation is that in blood stimulated in vitro with a wide range of immune agonists, including pathogen-associated molecular patterns, heat-killed bacteria and cytokines, the patterns of induction of PKM2, IL6 and IL1B at the transcriptional level are rather distinct:

• IL1B shows high induction by Heat-killed E. coli (HK E. coli), Staph (HKSA) and Legionella (HKLP) as well as Flagellin, PAM3, R837, Zymosan, CpG; and some induction by LPS, RSV and TNF. http://www.interactivefigures.com:80/dm3/miniURL/view/L3 (just in case here is a 20 sec video showing how to view the data: https://youtu.be/MAtDFnLeeG0)

• IL6 shows high induction by Heat-killed E. coli (HK E. coli – which dominates the responses) and some induction by Heat-killed Staph (HKSA) and Legionella (HKLP), Flagellin, PAM3, Zymosan and CpG http://www.interactivefigures.com:80/dm3/miniURL/view/L4

• As for PKM2, first, induction levels are not as dramatic; second strikingly no response is seen following culture with HK E. coli. Compared to the “ex-vivo control” (=culture without stimulation); the most induction is seen with HKSA and HKLP, with possibly some induction seen with LPS, Flagellin, PAM3, Zymosan or TNF http://www.interactivefigures.com:80/dm3/miniURL/view/L2

The explanation might be trivial (at least to you!), but I found such disconnect puzzling, especially with regards to differences in levels of induction by HK E. coli.

Also, would you assume that the induction of PKM2 transcription correlates with dimerisation and nuclear translocation?

If that were the case would this phenomenon be driven by ROS released as a result of an innate response to bacteria from for instance neutrophils, independent of a change in the cellular glucose metabolism?

Thanks!