Maternal immune activation (MIA) and Old World monkeys

Old World monkeys detailed in the title of this post, specifically refers to a type of animal called a rhesus macaque who were the 'participants' of choice as detailed in a recent study by Destanie Rose and colleagues [1] looking at a concept called maternal immune activation (MIA).

Those who followed this blog down the years will no doubt have seen me discuss MIA before in the context of autism and/or schizophrenia (see here for example). The basic theory is that whilst in-utero and enjoying approximately nine months in a warm and comfortable environment with a reprogrammed maternal immune system to stop a mother's body from 'rejecting' a developing foetus, infections encountered by the mother at critical periods of pregnancy might themselves or through their effects on the maternal immune system, have the ability to 'affect' offspring outcomes in a variety of ways. The majority of work on the concept of MIA has been in smaller animals such as rodents, so the inclusion of rhesus macaques is an important step as it was in other work with the immune system and autism in mind (see here).

So, take 21 pregnancy rhesus macaques and give them either "three injections over 72 hours of poly I:C-LC [an immune stimulant], a double stranded RNA analog (viral mimic), or saline as a control." Said injections were given either "near the end of the first trimester or near the end of the second trimester" to see whether timing of immune stimulation might be important. Macaque offspring were subsequently born and followed for about 4 years. Blood samples were collected from offspring "at the end of their first (year 1) and fourth (year 4) years to assess dynamic cellular immune function." At the same time, the behaviours of monkey offspring were also analysed to see if there were any effects from MIA exposure.

Results: behaviour did seem to be affected by MIA exposure, particularly stereotyped behaviours, noted to be a core feature of autism. Similarly, researchers reported some important immune system 'changes' associated with MIA exposure: "elevated production of innate inflammatory cytokines including: interleukin (IL)-1β, IL-6, IL-12p40, and tumor necrosis factor (TNF)α" at 1 year of age. Immune system changes were also noted longer-term at 4-years: "the MIA exposed offspring continued to display elevated IL-1β, and there was also a pattern of an increased production of T-cell helper type (TH)-2 cytokines, IL-4 and IL-13." Although being careful not to generalise too much when it comes to immune system markers and what they mean for pro- or anti-inflammatory signals, the leaning towards the production of Th-2 cytokines is typically linked to atopy and 'the promotion of IgE and eosinophilic responses in atopy.' The authors - including some notable names from the MIND Institute - conclude by suggesting that: "Data from this study suggests long-term behavioral and immune activation was present in offspring following MIA."

Accepting that animal models of something like MIA are not necessarily the same as human MIA and its responses, this is interesting work. If one however accepts the data on something like vaccine function being modelled in animals (see here for example) is akin to what happens in people, real people, there is some added strength to the information published by Rose and other groups on how MIA may indeed be a relevant factor when it comes to immune function potentially affecting offspring behaviour and development.

This research also intersects with quite a lot of other peer-reviewed science talking about how (human) pregnancy infection does seem to be related to offspring risk for conditions such as autism (see here). That various immune-related conditions such as asthma in mothers might also 'prime' for offspring neurodevelopmental issues is another important strand of research potentially pertinent to this area (see here). And then also there is the idea of an 'inflammatory autism subtype' (see here) also previously suggested continuing the important theme of immune function and behaviour/development being linked. There are, as you can see, quite a few potentially important connections that can be made between the Rose results and other data on MIA and offspring development.

Oh, and I'll be coming to the recent paper by Zerbo and colleagues all in good time...

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[1] Rose DR. et al. Long-term altered immune responses following fetal priming in a non-human primate model of maternal immune activation. Brain Behav Immun. 2016 Nov 19. pii: S0889-1591(16)30522-0.

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Rose, D., Careaga, M., Van de Water, J., McAllister, K., Bauman, M., & Ashwood, P. (2016). Long-term altered immune responses following fetal priming in a non-human primate model of maternal immune activation Brain, Behavior, and Immunity DOI: 10.1016/j.bbi.2016.11.020