So I’ve been clearly failing at keeping my promise of posting a semi-weekly update on the community about “3 things I learned last week”, but maybe this week I can make up for all of those missing posts by writing a brief daily summary of what’s happening at the EMBO Conference on hijacking host signalling and epigenetic mimicry during infections in Paris. The program is packed with great talks, but I can't possibly cover them all, so I’ll try to briefly mention a few of the things that really stuck to my mind (rather than providing a full account of events). Oh, and of course, if you’re also in attendance and see me walking around, please do stop me to say hi and let me know what you think of Nature Microbiology!
So for the first afternoon speakers really stuck to the theme of the meeting and there was a lot of talk about pathogens interfering with host epigenetic marks, including viruses, bacteria and parasites. 3 things I learned (or re-learned) were:
1. Salmonella is really ingenious. Jorge Galan started us up and showed a lot of unpublished data (so I won’t share many details) on how Salmonella manages to generate inflammation in the gut environment. Salmonella needs a bit of inflammation to drive pathogenesis and colonize the gut, but this is somewhat of a special location, as a lot of the innate immune receptors that are classically used to detect bacterial signals in other cells and tissues seem to be downregulated in the gut epithelium (potentially to avoid too much inflammation in response to bacterial products of the endogenous microbiota). So since Salmonella can’t really trigger inflammation at the receptor level, it has evolved some really cleaver ways to use type 3 secretion system (T3SS)-secreted effectors to interfere with signalling pathways downstream of the receptors. One nice example is mediated by SopA, which activates TRIMs downstream of RIG-I and MDA-5. This bypasses the need to trigger receptors to initiate signalling, but the end result is the same – the pathway is activated, and the host cells produce inflammatory molecules.
2. Hosts can be quite clever too. Harmit Malik revisited a published story that is just too cool not to share. It basically shows how genes encoding bacterial T6SS effectors have been horizontally transferred on multiple occasions to numerous eukaryotic hosts, including ticks and mites. These Type VI amidase effectors (Tae) can degrade peptidoglycan and are usually involved in mediating interbacterial competition, but by acquiring and further evolving these genes, hosts have basically gained a new immune mechanism of defense against bacteria.
3. Toxoplasma carries an arsenal of effectors. Mohamed-Ali Hakimi discussed a lot of studies from his lab on Toxoplasma effector proteins and how they alter the function of infected cells. He talked about how GRA24 sustaines host p38 MAPK activation; how TgIST dampens STAT1-dependent gene regulation and IFN-γ-mediated host defences; how GRA16 alters gene expression; and briefly on how GRA26 and GRA28 may be working as well. He was then asked about why Toxoplasma should need to carry so many different effectors with multiple subversion strategies, and although the answer is still up for grabs, it could possibly have to do with the need of the parasite to modulate different pathways at different stages of infection (acute vs chronic), in different cell types, and in different tissues. But examining these temporal and spatial requirements in vivo is not an easy task.
Ok, that’s the 3 things for today – hopefully I can find the time to update you on tomorrow’s developments soon.