T.gondii and dietary gluten joining forces?

Looking back at the way this blog has taken shape over the nearly two years that its been running, certain topics have tended to predominate which I freely admit that I knew very little about before getting into this blogging malarky.

Cold cat @ Wikipedia  

Had anyone suggested that one day I would be reading and writing about critters like Toxoplasma gondii (T.gondii to its friends), I previously would have replied 'yer what?' with puzzling facial expression to match.

Nevertheless I have found myself drawn into discussing research on this survivor and in particular how it might do so much more than just infest quite a few people around the world with particular focus on its potential role in conditions like schizophrenia, or at least some cases.

Enter then another study by a familiar name to this blog, Emily Severance and colleagues* (open-access) discussing T.gondii and some interesting possibilities on how it might be able to alter the immune response to dietary gluten, in mice, with potential implications for schizophrenia and even autism.

The research of Dr Severance and colleagues, as mentioned, has appeared twice on this blog so far as per posts on gastrointestinal (GI) inflammation in cases of schizophrenia (see here) and C1q activation (see here). I was particularly impressed with the GI inflammation paper it has to be said, not least because it introduced a really interesting investigative tool (anti-Saccharomyces cerevisiae IgG antibodies) which I thought could easily be looked at with autism in mind.

To the more recent paper:

• Aside from one of our papers getting a mention (thank you!), the study aimed to look at how infection with T.gondii might impact upon the way the immune system recognises and deals with the dietary protein gluten in a mouse model, in a sort of infection-changing-immune-system type way.
• Balb/C mice were infected with T.gondii via one of three routes: intraperitoneal (IP), peroral (PO) (via oral-diet), or prenatally.
• Antibodies (IgG) to T.gondii, gluten and C1q were measured.
• Results: I seem to say this everytime, but lots of results were generated. Perhaps the most important was the finding that infection with T.gondii was 'convincingly' (author word not mine) related to the production of gluten antibodies. 
• Second in importance was the finding that prenatal exposure to T.gondii as in the offspring of female mice who were infected, showed an elevation of antibodies to T.gondii when mummy mouse was seropostive for T.gondii which also coincided with very significantly elevated antibodies to gluten and C1q. Also, the "female sex is more severely affected following T. gondii infection".
• Finally(!) there is a suggestion of some involvement for gut hyperpermeability (the so-called leaky gut) in this story, as per the question of "how T. gondii strains gain access to systemic circulation, but a para-cellular route affecting epithelial tight junction proteins is suspected". And even those words "bacterial translocation" and "zonulin" are mentioned as part and parcel of how T.gondii might be able to open up the gut membrane and potentially allow gluten peptides to come into contact with the immune system. Not a million miles away from what's been talked about with autism in mind previously.

And rest. So, we are presented with lots of potentially important statements here concerning how infection might combine to promote an immune response to an important dietary component like gluten. We are also given a hint that maternal infection might also lead/cause/be associated with an immune response to dietary gluten in offspring. Sounds to me like some quite important leads there and more than a passing relationship with other work looking at immune activation models of conditions like autism (hint: Paul Patterson and colleagues). I also wonder whether there may be other, wider considerations of maternal immune activation as per those findings on maternal antibodies to foetal brain and the transglutaminase research in autism.

With the old science hat on, I have to reiterate that this was a study of mice not humans, and as far as I can remember these results are slightly at odds with the other C1q activation and T.gondii data previously presented**. Independent replication is also required, but I'm not going to take anything away from these very, very interesting findings which perhaps mirror other findings of infection triggering antibody production*** (many thanks to Natasa for this last link).

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* Severance EG. et al. Anti-gluten immune response following Toxoplasma gondii infection in mice. PLoS ONE. 2012; 7(11): e50991.

** Severance EG. et al. Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia. Neurobiol Dis. 2012; 48: 447-453.

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Emily G. Severance, Geetha Kannan, Kristin L. Gressitt, Jianchun Xiao, Armin Alaedini, Mikhail V. Pletnikov, & Robert H. Yolken (2012). Anti-Gluten Immune Response following Toxoplasma gondii Infection in Mice PLoS ONE : doi:10.1371/journal.pone.0050991