Quorum sensing effect in the immune system

I would like to point out one of my recent publication about quorum sensing in the immune system. I explored the hypothesis of existence of quorum sensing like mechanism in the immune system. This work aim to motivate immunologist to think more of population dynamic in the immune system. It was done during the year after my PhD during my research assitant position at College de France.

It was not easy to publish a hypothesis paper like this one has a young researcher. Even if the work is not completly mature, it is nice that there is some journal that accept to publish such work.

References:

Does a quorum sensing mechanism direct the behavior of immune cells? Comptes Rendus Biologies. Volume 336, issue 1, January 2013, Pages 13-16

link to the publication on the publisher’s website

link to the unedited version on my website

L’hématopoïèse à l’échelle unicellulaire

I am honoured to be the next guest of the philosophy and immunology seminar series (that I created 3 years ago before leaving to the Netherlands). The session will be done in French, here is the information about the seminar.

La prochaine séance du séminaire Philosophie & immunologie aura lieu le 21 février 2013, 17h-18h30 (merci de bien noter l’horaire inhabituel), à l’IHPST :

L’hématopoïèse à l’échelle unicellulaire : changer d’échelle et de regard sur un processus biologique grâce au code-barre cellulaire

Résumé :
L’hématopoïèse est définie comme le processus de différentiation qui conduit à la production des cellules sanguines à partir des cellules souches hématopoïétiques. Cette différentiation a été étudiée sur des populations de cellules et est classiquement représentée sous forme d’un arbre de différentiation. Les branches de l’arbre conduisent à la production des cellules immunitaires et des autres cellules sanguines par diversification de leurs précurseurs. Deux lignées principales divergent à la base de cet arbre : une lignée myéloïde et une lignée lymphoïde.
L’avancée technologique des code-barres cellulaires, nous permet d’étudier ces processus de différentiation non plus simplement à un niveau global, mais à l’échelle des cellules individuelles. Or, nos récents résultats expérimentaux remettent en cause l’arbre de différentiation tel qu’il a été accepté au cours de ces dix dernières années. Cet exposé se propose de discuter en quoi un changement d’échelle technique et conceptuelle dans l’étude des objets biologiques amène à repenser en profondeur un processus biologique tel que la différentiation. En s’appuyant sur une définition généalogique de la lignée plutôt que moléculaire ou génétique, la technique des code-barres cellulaires révèle ainsi l’existence d’une troisième lignée, producteur des cellules dendritiques. Par ailleurs nos résultats couplés à de la modélisation mathématique suggèrent que le processus de différentiation ne suivrait pas des voies uniques (« les branches de l’arbre ») mais emprunterait des voies multiples. Nous discuterons des implications théoriques de ces résultats en soulignant la nécessité d’une recherche de nouvelles analogies pour exprimer de façon appropriée un nouveau regard sur ces processus.

Lectures conseillées :
–  La technique des codes barres cellulaires : Nat Rev Immunol. 2010 Sep;10(9):621-31. Mapping the life histories of T cells. Schumacher TN, Gerlach C, van Heijst JW.
–  Histoire de la découverte des cellules souches hématopoïétiques :
Stud Hist Philos Biol Biomed Sci. 2007 Mar;38(1):217-37. Epub 2007 Feb 12.The search for the hematopoietic stem cell: social interaction and epistemic success in immunology. Fagan MB.

Ed Cohen seminar on the 13rd of march 2012

The next Philosophy & Immunology, that I can’t organized anymore from the Netherlands, will  received

Ed Cohen, Université de Rutgers, USA (http://womens-studies.rutgers.edu/faculty/core-faculty/122-ed-cohen) :

on the 13rd of mars 2012, at noon.

It sounds to be challenging! If you are in Paris at that time, you should definitly go!

“If Immunity Doesn’t Exist Is It Still Real? or, A Vital Paradox”

Abstract :

At the end of the 19th century biology and medicine recruited an ancient legal and political concept, “immunity,” to describe what they newly recognized as an essential physiological function of multi-cellural organisms, “defense,” another concept which not coincidentally also had it’s own long legal and political history. Indeed, when Eli Metchnikoff introduced the rubric “immunity-as-host-defense” into bioscience, he actually combined two contradictory terms (i.e., juridically speaking where immunity exists there is no need of (legal) defense, and conversely where a defense is needed there is no immunity) in order to encompass what he imagined as the complex organism’s response to microbial “invasion.” While this formulation proved essential in making sense of the “germ theory of disease” promoted by Koch and Pasteur among others, it also imported a number of philosophical and political assumptions into biomedicine that may not have been warranted by the empirical observations themselves. In particular, Metchnikoff’s hybrid immunity-as-host-defense invoked a specific set of axioms derived from liberal political philosophy in order to affirm that multi-cellular organisms actively conserve their own integrity by defending what is “properly” their own–or even, what is their own “property”–at the cellular level. (Paul Ehrlich, who shared the 1905 Nobel prize with Metchnikoff, would then extend this precept to the molecular level via the concept of “specificity” a decade or so later.)

Fifty years after Metchnikoff first posited immunity as host defense, MacFarland Burnet transformed the field of immunology into the “science of self/non-self discrimination.” In so doing he rendered the notion of the defended organism theoretically plausible by asserting “the self” as the both ontological and epistemological ground of the organism. While the experimental programs that resulted from immunology’s embrace of S/NS discrimination have produced numerous significant insights both about how organisms of different scales co-exist in shared spaces and about how multicellular organisms persist in time, Burnet’s assertions (like Metchnikoff’s) incorporated a number of assumptions that may not have derived either from his experiments themselves or from scientific discourse more generally, but may instead have ensued from the political and philosophical frameworks within which he worked. 

Recently a number of exciting new immunological theories have challenged Burnet’s S/NS doctrine in order to reconsider several persistent impasses in immunological thinking: e.g., autoimmunity, host-versus-graft disease, cancers, pregnancy, and commensal organisms. However, despite the exciting possibilities that these theories present for immunological thought and practice, they nevertheless seem to share a conceptual opacity that has endured since Metchnikoff and Erlich first construed immunity as a robust scientific concept: i.e., they fail to appreciate that immunity is always already a paradoxical term. In fact, in its juridical and political valence, immunity was created precisely in order to rectify the constitutive tensions between the formal structure of the law and the empirical messiness of political life. In other words, immunity was legally invented in order to maintain the fiction that the law’s jurisdiction is universal by creating legal exceptions that affirm the law’s universality even while acknowledging–and moreover finessing–the particular political exigencies that the law inevitably must exempt. 

Unfortunately when biology and medicine incorporate immunity as an organizing principle for their activities they by and large ignore the concept’s foundational status as a paradox. Instead they usually seek to contain the effects of this foundational paradox by construing it in terms of mutually exclusive oppositions (inside/outside, self/not-self, dangerous/not-dangerous, continuous/discontinuous, etc.) thereby displacing the troubling perturbations to which immunity actually gives rise. In this talk, I will try to suggest that whatever it does at the cellular, molecular, or even quantuum-mechanical levels, biological “immunity” as such may not exist insofar as it always “is” paradoxical–which does by any means imply that it is not real. Rather it may be worth considering whether what we have come to call biological immunity in fact specifies the paradox that living organisms must be insofar as they must be simultaneously open and bounded in order to live at all. Following Francisco Varela’s reflections on the “intriguing paradoxicality proper to an autonomous identity,” which he attributes to the fact that “the living system must distinguish itself from the environment while at the same time maintaining its coupling,” this talk will wonder if it could be interesting to consider that biological immunity might “be” precisely that which makes this vital paradox both possible and liveable.

Natural infection in mouse house: an opportunity or a problem ?

Today in my lab, an infection (Spironucleus muris) has been diagnosed on the mice of our animal facility. The bad news is that infection will ruin all the results from immunological studies because the infection will interfere with the immunological process we wish to study.

Having an infection in animal facilities is quite well-known phenomena for a “mouse” immunologist (an immunologist who performs experiment with mice) but is new for me.  Before I used to work on human cells and organs.

Rather than being desperate, it brings me some fresh air. It is an occasion to study a natural infection. For those of you who are not familiar with immunology, if you were looking at our protocol you could imagine chicken ovalbumine is the worst cause of infection on Earth. Ovalbumine is indeed used as a model in immunology because mice don’t eat chicken and it is supposed that they have never been exposed to chicken protein. As a result, you can control better your experimental setup. Moreover ovalbumine is easy to produce in large quantity as it is the main component of eggs.

A natural infection could be seen as a real opportunity. First, it allows to study the ecology of an infection in mice in a lab. It could be a model as good as ovalbumine. I was really disappointed not to find more articles on that topic on pubmed. Immunologists could try to develop vaccines or treatments for mice.. Moreover we could think that having a patent  and selling a treatment or vaccine could finance your research as the problem is not isolated.

War or Police metaphor in immunology?

I am concerned about the use of the police and war metaphor in immunology; you can have a look at my previous post. I find it very difficult to think outside of this specific box. We are taught immunology with this metaphor. We told to communicate about immunology with this metaphor. I have the feeling that I face a wall when I try to think differently.

When you try to avoid the political extremism of this metaphor, it is difficult not to go into an other extreme, into a caricature of the opposite position. Indeed, we could be tempted by a peace and love metaphor (ref 1), but this would  be such a caricature.

I chose here to take a political direction to give an example of a way to rethink the metaphor. I agree that science should avoid politics. But today for the sake of thinking outside of the book, I will assume my political positions and explore new avenues.

In this case, my vision of the immune system is a system that maintains homeostasis. We can push further away Michod idea about the role of the immune system in the emergence of multicellularity (ref 2). I will propose that the immune system plays a role in the maintenance of this multicellularity.  We can draw a parallel between this maintenance and human social cohesion systems. In this case the immune system could not only be the police, but also social security? Justice? Moreover if we consider that citizenship can be achieved through local social cohesion, then several different actors can play a role depending on the local condition. Maybe this can help us understand why we have difficulties to define the actors of the immune system. They change depending on the local environment, such as epithelial cells.

Of course, this is a first idea that needs to be further developed. I hope you will be interested and I am waiting for your friendly suggestions.

References:

1. Ed Cohen. Metaphorical Immunity.  Literature and Medicine 22. 2003.

2. Richard Michod & Denis Roze, Cooperation and conflict in the evolution of multicellularity, Heredity, 2001.

immunology and philosophy seminar= from botryllus model revisting immunology?

Chères amies, chers amis,

La prochaine séance du séminaire “Philosophie & immunologie” aura lieu le mercredi 15 décembre, de 12h à 13h30, à l’IHPST.

Nous aurons le plaisir d’accueillir Anthony De Tomaso, professeur à l’Université de Californie-Santa Barbara (Département de biologie moléculaire, cellulaire et développementale), pour un exposé intitulé :

Allorecognition in a basal chordate: education, tolerance, and the origins of missing-self recognition

Anthony De Tomaso est un spécialiste internationalement reconnu de l’organisme colonial Botryllus schlosseri,
l’un des exemples les plus passionnants pour tous les biologistes et philosophes intéressés par la question de l’individualité biologique. De Tomaso a étudié le développement, l’immunité et l’histocompatibilité de
cet organisme colonial, en démontrant en 2005 le fonctionnement de la fusion et du rejet entre deux colonies de Botryllus. Il a également mis en évidence une forme de parasitisme par des cellules souches suite à la
fusion de deux colonies de Botryllus.

Abstract:

Histocompatibility is the ability to discriminate self from non-self tissues, with examples found in nearly all metazoan phyla, from marine sponges to mammals. This process is initiated by a natural or experimental mixing of tissues from different genotypes, which are either accepted, forming a chimera, or rejected, during which the interacting tissues are destroyed. This process ultimately relies on the discrimination of highly polymorphic ligand(s), but how specificity is achieved is not well understood. In the vertebrates, allorecognition is a function of immunity and is mainly due to polymorphisms of the major histocompatibility complex (MHC) proteins, recognized by effector cells in both the adaptive (T-cells) and innate (Natural Killer (NK) cells) branches of the immune system. However, despite the phenotypic similarities of allo-responses between higher vertebrates and other metazoans, there is no conservation of the ligands and receptors: orthologs of the MHC, T-cell receptor, and NK receptor genes cannot be found in either jawless fish, lower chordates or invertebrates; and candidate histocompatibility genes in species below the jawed vertebrates are not even homologous to each other, even within the same phylum. Thus, while it is clear that the ability to discriminate between polymorphic histocompatibility ligands has an early evolutionary origin, the molecular and cellular basis of specificity and any potential conservation of this complex process remain enigmatic.

Botryllus schlosseri is a colonial ascidian with an experimentally-accessible allorecognition system. Allorecognition takes place at the tips of an extracorporeal vasculature which can results in vascular fusion (parabiosis) or a blood-based inflammatory rejection which blocks fusion. Fusion or rejection is determined by the polymorphisms of a single protein, called the fuhc with the following rules: two colonies will fuse if they share one or both fuhc alleles, and reject if no alleles are shared. Functionally, this is reminiscent of the missing-self recognition found in vertebrate NK cells and it has been shown that this recognition event is highly discriminatory: the effector system can recognize a self-fuhc allele from hundreds and potentially up to a thousand competing alleles However, the molecular and cellular basis of this discriminatory ability is unclear. Our lab has been dissecting the molecular mechanisms which underlie allorecognition in Botryllus, and recently identified a receptor family involved in this interaction. Functional analysis reveals that allorecognition consists of independent pathways which control compatible and incompatible outcomes, each controlled by a different receptor. The signals from each pathway are integrated within the interacting cells, and an output is decided.  My talk will focus on this integration of signals, and recent unpublished data which suggests that the ability to discriminate between highly polymorphic ligands is conserved, but this conservation is not at the level or receptors and ligands, but rather how in how a cell responds to extracellular stimuli- including during development (education) and over the life of an organism (tolerance). I will also discuss why allorecognition is so widespread among multicellular organisms.

Principales publications :

• Brown, F.D., Tiozzo, S., Ishizuka, K., Swalla, B.J., and De Tomaso A.W. (2009) Early lineage specification of long-lived germline precursors in the colonial ascidian, Botryllus schlosseri. Development 136:3485-3494.
• Nyholm, S.V., Passegue, E., Ludington, W., Voskoboynik, A., Mitchel, K., Weissman, I.L., and De Tomaso, A.W. (2006) fester, a candidate allorecognition receptor from a primitive chordate Immunity 25:163-173
• Laird, D.J., De Tomaso, A.W., and Weissman I.L. (2005) Stem cells are units of natural selection in a colonial ascidian. Cell 123:1351-1360.
• De Tomaso, A.W., Nyholm, S.V., Ishizuka, K.I., Palmeri, K.P., Ludington, W.B., Mitchel, K and Weissman, IL Isolation and characterization of a protochordate histocompatibility locus. Nature 438:454-459. (2005)
• De Tomaso, A.W., and Weissman, I.L. (2004) Evolution of a protochordate allorecognition locus Science303:977.

Lieu : IHPST, Grande salle,
13 rue du Four
2e étage
75006 Paris
(M°Mabillon ou Saint-Germain)