How do microbial biofilms evade the immune system?

Microbial biofilms are a major medical problem. While the immune system is excellent at picking off individual yeast or bacteria, when these pathgoens band together into a multicellular biofilm they gain the ability to evade the immune system. In a study just out in Frontiers of Immunology, we come up with a theoretical framework to understand how this immune evasion occurs. There are three basic models by which the biofilm could evade the immune system: 1) it could be immunologically silent, using the biofilm as a barrier to make sure that no microbial products leak out to alert the immune system; 2) it could trick the immune system, creating new products that get the immune system to attack in the wrong way; or 3) it could resist the immune system, using the biofilm to block the attack by host cells. By using a mouse model of Candida biofilm infection we were able to demonstrate that the third model is correct - the biofilm is neither silent or diverting, permitting the generation of an effective anti-Candida immune response. Instead, the biofilm acts to somehow block the immune attack on any cells that stay within the biofilm. These findings will allow researchers to focus on understanding the molecular mechanism of biofilm immune resistance, hopefully one day contributing to new treatments for biofilm infections.

Original study: A Framework for Understanding the Evasion of Host Immunity by Candida Biofilms. Garcia-Perez et al. 2018. Front. Immunol., https://doi.org/10.3389/fimmu.2018.00538

Having Kids Radically Reshapes Parents’ Immune Systems

Imagine this: The love of your life is 10 inches shorter than you. This being a non-issue, the two of you get on with moving in together and starting a small brood of young humans of your own. Over time, something a little strange starts to occur. You seem to be shrinking just as your partner spurts up. When the dust settles, you maintain the height advantage but the distance between you is cut in half, down to just five inches.

This is analogous to what happens to your immune system when you co-parent. “You are completely changing the cells that constitute your immune system in a way as radical as changing your height,” says Adrian Liston, a researcher at the Translational Immunology Laboratory at VIB in Belgium.  In 2016, Liston was part of the team that documented the physical composition of co-parents’ immune cells shifting to resemble their partners’ cells. Eventually, he says, co-parents end up with more in common immunologically than identical twins.

Are these changes for better or for worse? It’s a tough question to answer, because parenting brings both benefits and deficits. More critically, though, there is no such thing as an ideal immune system — their strength is in their diversity, and between healthy individuals it’s hard to say if one setup is better than another setup. Basically, it depends entirely on the context of what you need your immune system for, and what you need it to do.

It’s clear, however, that becoming a parent changes you fundamentally. Now we know that those changes take effect at the cellular level and define the structure of your inner defense systems. There’s still more we don’t know than we do about how this works, but here are five factors that likely affect it.

 Read the full article in Fatherly.

An interview with Stephanie Humblet-Baron

An interview between Dr Liesbeth Aerts and Dr Stephanie Humblet-Baron on her recent paper in JACI:

Can you summarize the significance of your findings in a few sentences for people outside your field?

Working in the field of primary immunodeficiency disorders, we described a new mouse model for severe combined immunodeficiency (SCID), recapitulating the key clinical features of SCID patients suffering of both immunodeficiency and autoimmunity (leaky SCID). Importantly our model proposed a novel efficient therapeutic approach for this disease.

What made the paper particularly outstanding?

Due to the pre-clinical evidence of a drug efficiency to treat a rare disease, patient clinical trials can be directly proposed. This treatment is already approved for human use in arthritis, so it could be rapidly be repurposed for leaky SCID patients. In addition, our model is available for further pre-clinical assay, including gene therapy.

When did you realize you were on to something interesting?

When I started to work with this model I already knew which gene was mutated (Artemis). However when I saw the mice for the first time I could tell that they were developing the exact same symptoms that we see in the clinic. I knew that other mouse models working on this gene had never seen leaky SCID symptoms, so I knew we needed to explore in depth the model. The other key moment was after treating our mice with the drug (CTLA4-Ig) – it completely blocked disease, making this a very valuable project with new therapeutic opportunities for patients.

Did the technology available at the department make a difference?

The FACS core was the major technique used for investigation this project.

A huge amount of work and energy must have gone into the paper. How did you cope with stress and doubts?

Liesbeth this is a joker question!

The project went actually quite smoothly, the hard time I got during this project was rather adjusting myself with motherhood and life in science at the same time.

What are you personally most proud of?

This work can be seen as translational medicine, with direct therapeutic benefit for the patients. The ability for better understanding the mechanism of the disease was also valuable to me.

Can you share some advice for others?

Always envision your project as a story to write and tell. When you find a new result ask what would be the next question and continue to explore it further.

Commercial staining kits

Foxp3 staining is notoriously difficult. The original protocols did not work, and it was a major breakthrough when BD and eBio released fix/perm kits that allowed good Foxp3 staining. The companies keep the formula secret, so that you have to buy from them, but it turns out 0.1% dishwashing liquid works just as well...

Belgian Immunology Society meeting 2017

This year the Belgian Immunology Society meeting was hosted by the Translational Immunology laboratory in Leuven, with the theme "immune regulation". We had record attendence, with dedicated sessions on fundamental immunology, clinical immunology, neuroimmunology and tumour immunology. Great morning talks by Belgian scientists, an interactive poster session, and an afternoon keynote session with outstanding presentations from Anne Puel (INSERM, France), Denise Fitzegerald (QUB, UK), Gabriele Bergers (VIB), Anne Dejean (Toulouse, France) and Gitta Stockinger (Crick Institute, UK). I certainly learned a lot of immunology on the day!

Many thanks to our scientific coordinators and session chairs: Susan Schlenner (KUL), Niels Hellings (Hasselt), Erika Van Nieuwenhove (UZ Leuven) and Abhishek Garg (KUL). The meeting would not have been such a success without Wim Cockx, Caroline Lenaerts and all the volunteers from the lab who helped out on the day.

Great support from our sponsors made it all happen:

Platinum sponsor: BD Bioscience

Silver sponsors: ThermoFisher, Stem Cell Technologies, Sanbio, BioLegend, Bioconnect, Analis, Miltenyi Biotech

Bronze sponsors: VWR, biotechne

Presentation of the EFIS-IL lecture award to Prof Gitta Stockinger (Crick Institute, UK) by BIS President Oberdan Leo. 

Jobs, jobs, jobs!

Two post-doc positions now open in immunology, plus a technician position in the FACS Core, and very soon we will be opening up a new position in endocrinology!

Immunology Group of Victoria

The 2017 IgV meeting in the Yarra was a beautiful reminder of what a vibrant and friendly community Australian immunology is. Top level science in one of the most  internationally creative hubs for medical research, coupled with a whole lot of fun. Perfect.

Factchecker: 'De Belg is steeds minder resistent tegen bacteriën'

‘Belg is steeds minder resistent tegen bacteriën’

Jan Jagers Uit Knack van 16/08/17

Ondernemer Kurt Van Tendeloo (Hygieia), Gazet van Antwerpen

De afgelopen weken hadden opvallend veel jongeren op bivak te kampen met maag- en darmproblemen. ‘In deze periode woekeren bacteriën meer dan anders’, zei Kurt Van Tendeloo daarover in Gazet van Antwerpen. Zijn bedrijf Hygieia geeft advies over voedselveiligheid en allergenenbeheer, en gaf dat ook al aan jeugdverenigingen specifiek voor op kamp, lazen we in de krant. ‘De dioxinecrisis heeft van België een land met extreme aandacht voor voedselveiligheid gemaakt’, zei Van Tendeloo. ‘Positief, maar hierdoor is de Belg minder resistent geworden omdat we zo weinig met bacteriën in aanraking komen. Vroeger werden kinderen ook ziek op kamp, maar niet met twintig tegelijk.’

Dat ons overmatig antibioticagebruik bacteriën doet muteren waardoor die geneesmiddelen almaar minder goed werken, is een gekend probleem. Wat Van Tendeloo zegt, gaat evenwel niet over antibioticaresistentie, maar over ons immuunsysteem. Is de ‘Belg steeds minder resistent tegen bacteriën’, zoals Gazet van Antwerpen kopte? Waarop steunt die uitspraak?

‘Niet op wetenschap’, zegt aan de telefoon Van Tendeloo, die kok is van opleiding. ‘Maar ik sta al meer dan twintig jaar in het vak, in grootkeukens, en zetel met actuele kennis van zaken in commissies die de voedselveiligheid daar bewaken. Voedselveiligheid is van levensbelang, in het bijzonder bij kwetsbare groepen zoals kinderen of senioren. Maar de appel die vroeger thuis op de grond viel, werd afgewassen en toch opgegeten. Vandaag niet meer. En dat breekt ons zuur op.’

Leert dat ook de wetenschap? We komen inderdaad minder in aanraking met bacteriën en allergenen, allerhande stoffen en microben die ons afweersysteem prikkelen, zegt viroloog Marc Van Ranst (KU Leuven). ‘Het aantal keizersneden is gestegen, moeders geven meer flessenvoeding dan vroeger, en we groeien meer op in stadsomgevingen dan op de boerderij’, zegt hij. ‘Het aantal allergieën is de afgelopen twintig jaar verdubbeld. Dat verklaren een aantal wetenschappers – er is discussie – met de zogeheten hygiënehypothese, die zegt dat contact met allergenen in onze jeugd cruciaal is, om later allergieën te voorkomen.’ Maar een maagdarminfectie is geen allergie, beklemtoont Van Ranst. ‘Vandaag halen die opgebroken jeugdkampen de media, maar niets wijst erop dat er meer incidenten zouden zijn dan vroeger. Die jongeren zijn hoogstwaarschijnlijk geteisterd door een norovirus. Een derde van alle mensen is daartegen genetisch resistent, twee derde wordt er ziek van. Dat is de grootte van zo’n epidemie als je die z’n gang laat gaan. Honderd jaar geleden was dat zo. En dat is vandaag niet anders.’

We zijn meer gevaccineerd tegen aandoeningen waaraan kinderen vroeger stierven – denk aan polio, mazelen, rode hond – en in die zin net weerbaarder, voert Van Ranst nog aan.

Maar ook als we die kinderziektes buiten beschouwing laten, is er meer tegen dan voor Van Tendeloo’s claim. ‘Het aantal bacteriële doden stijgt niet’, zegt immunoloog Adrian Liston (KU Leuven). ‘Wel is er een verschuiving bezig. Het klopt dat ons afweersysteem het moeilijk heeft met uitdagingen die het niet vaak tegenkomt. Aangezien we almaar meer in steden wonen en minder op het platteland, worden we gemiddeld minder goed in het neerslaan van rurale infecties – tegen grondbacteriën zoals Legionella, bijvoorbeeld – en beter in het afweren van infecties die mensen op elkaar overdragen. Maar in slotsom zijn we sterker dan ooit tevoren.’

Conclusie:

Omdat we volgens wetenschappers geen systematisch probleem hebben met neerslaan van bacteriën, beoordeelt Knack de stelling als grotendeels onwaar.  

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Ways to succeed in science

Hidde Ploegh, Harvard/MIT, finished his lecture today with a message to the PhD students:

If you can buy it out of a catalog, you can assume that all the obvious experiments have been done. You will not make a major discovery or make an impact in the field until you develop new tools. You need to be willing to take a risk and invest in designing and building new strategies to look at old questions.

Very good advice, of course, coming from someone who has been incredibly successful in just this manner. There are many great immunologists who have made their mark in this way; Pippa Marrack and Gary Nolan spring to mind.

I would say that it is not the only way to be incredibly successful though. I tend to think of three basic types of high level success in science:

• The builder. In the vein of Ploegh, Marrack or Nolan, they constantly build new technology or techniques to push back the boundaries of the possible
• The bridger. There are many "builders" out there, working in different areas. And the tools created for one purpose always have great potential in other areas. The bridger is someone who keeps an open mind and an eye on many fields, looking for the opportunity to pull in a new approach or idea from another field into their own arena. Researchers like Diane Mathis, Sasha Rudensky and Jean-Laurant Casanova have been very successful in rewriting their field without inventing new technology. 
• The thinker. Perhaps the rarest is the person who thinks of a simple elegant experiment that could actually have been done decades ago, but just wasn't. Not every advance relies on the brute force of new tech, some just need another way of looking at the problem. I see Gita Stockinger, Polly Matzinger, Ruslan Medzhitov and Chris Goodnow as successful in this approach. 

Of course, many of the best use aspects of each approach, and I am sure there are other models too.