Trans-generational Immune Priming Protects the Eggs Only against Gram-Positive Bacteria in the Mealworm Beetle

In many vertebrates and invertebrates, offspring whose mothers have been exposed to pathogens can exhibit increased levels of immune activity and/or increased survival to infection. Such phenomena, called “Trans-generational immune priming” (TGIP) are expected to provide immune protection to the offspring. As the offspring and their mother may share the same environment, and consequently similar microbial threats, we expect the immune molecules present in the progeny to be specific to the microbes that immune challenged the mother. We provide evidence in the mealworm beetle Tenebrio molitor that the antimicrobial activity found in the eggs is only active against Gram-positive bacteria, even when females were exposed to Gram-negative bacteria or fungi. Fungi were weak inducers of TGIP while we obtained similar levels of anti-Gram-positive activity using different bacteria for the maternal challenge. Furthermore, we have identified an antibacterial peptide from the defensin family, the tenecin 1, which spectrum of activity is exclusively directed toward Gram-positive bacteria as potential contributor to this antimicrobial activity. We conclude that maternal transfer of antimicrobial activity in the eggs of T. molitor might have evolved from persistent Gram-positive bacterial pathogens between insect generations.     

Facultative but persistent trans-generational immunity via the mother's eggs in bumblebees

It is widely acknowledged that a mother, and the maternal environment, can have a profound effect on the phenotype of her offspring. For example, immunocompetent vertebrate mothers can pass on immune factors to their otherwise immune na?ve offspring. Recently, it has also been demonstrated in invertebrates that maternal contact with pathogens and immune elicitors can have a positive impact on offspring resistance and immune system components. Here, using a cross-fostering design, we show that trans-generational immune priming in a social insect, similar to birds, takes place through factors in the eggs, with effects persisting into adult worker offspring. Additionally, eggs from immune-challenged mothers are imbued with increased internal antibacterial activity when they are laid.     

Trans-generational immune priming in a social insect

Detecting functional homology between invertebrate and vertebrate immunity is of interest in terms of understanding the dynamics and evolution of immune systems. Trans-generational effects on immunity are well known from vertebrates, but their existence in invertebrates remains controversial. Earlier work on invertebrates has interpreted increased offspring resistance to pathogens as trans-generational immune priming. However, interpretation of these earlier studies involves some caveats and thus full evidence for a direct effect of maternal immune experience on offspring immunity is still lacking in invertebrates. Here we show that induced levels of antibacterial activity are higher in the worker offspring of the bumblebee, Bombus terrestris L. when their mother queen received a corresponding immune challenge prior to colony founding. This shows trans-generational immune priming in an insect, with ramifications for the evolution of sociality.     

Carotenoids and egg quality in the lesser blackbacked gull Larus fuscus: a supplemental feeding study of maternal effects.

Egg quality is a phenotype of, and can profoundly influence fitness in, both mother and offspring. However, the physiological mechanisms that underlie this maternal effect are poorly understood. Carotenoids are hypothesized to enhance antioxidant activity and immune function, and are responsible for the pigmentation of egg yolk. The proximate basis and consequences of this maternal investment, however, have not previously been studied in wild birds. In this supplemental feeding study of lesser black-backed gulls, Larus fuscus, carotenoid-fed females are shown to have increased integument pigmentation, higher plasma concentrations of carotenoids and antioxidant activity, and lower plasma concentrations of immunoglobulins (Igs) in comparison with controls. In turn, carotenoid-fed females produced eggs containing high carotenoid but low Ig concentrations (i.e. passive immunity), whereas control females produced eggs containing low carotenoid but high Ig concentrations. Within-clutch patterns of these resources varied over the laying sequence in a similar manner in both carotenoid-fed and control nests. Our results suggest that carotenoids could be one resource responsible for egg quality maternal effects in birds. We discuss the possible implications of carotenoid-mediated effects on phenotype for fitness in mothers and their offspring.     

Mother guarding: how offspring may influence the extra-pair behaviour of their parents

In this paper we propose a novel form of social control of mate choice. Through mother guarding, offspring can help in protecting the paternity of their father by preventing their mother from engaging in extra-pair matings. We present a model that predicts the circumstances under which mothers should be selected to seek or avoid extra-pair matings, and existing offspring should be selected to prevent or promote such matings. In its simplest form, our model shows that offspring are selected to mother guard as long as the viability of extra-pair young is less than twice that of within-pair young; when the relative viability is greater, offspring are selected to promote extra-pair mating by their mother. If the existing offspring are not necessarily sired by their mother's social mate, then the potential for conflict is further reduced. We also consider whether offspring have an interest in the extra-pair reproduction of their fathers. We show that when the costs of the father's infidelity to the mother's brood are high, existing offspring are selected to prevent extra-pair mating by their father; when such costs are low, offspring are selected to promote extra-pair mating by their father. In principle, our model applies to all species where offspring show delayed dispersal and where breeding pairs raise multiple broods or litters. This situation exists in, but is not limited to, the majority of cooperatively breeding species. The significance of this model with regard to our current understanding of the evolution of extra-pair behaviour in such species is discussed.     

Allometric scaling of the elevation of maternal energy intake during lactation

The amount of resources provided by the mother before birth has important and long-lasting effects on offspring fitness. Despite this, there is a large amount of variation in maternal investment seen in natural populations. Life-history theory predicts that this variation is maintained through a trade-off between the benefits of high maternal investment for the offspring and the costs of high investment for the mother. However, the proximate mechanisms underlying these costs of reproduction are not well understood. Here we used artificial selection for high and low maternal egg investment in a precocial bird, the Japanese quail (Coturnix japonica) to quantify costs of maternal reproductive investment. We show that females from the high maternal investment lines had significantly larger reproductive organs, which explained their overall larger body mass, and resulted in a higher resting metabolic rate (RMR). Contrary to our expectations, this increase in metabolic activity did not lead to a higher level of oxidative damage. This study is the first to provide experimental evidence for metabolic costs of increased per offspring investment.     

Maternal transfer of resistance to Schistosoma mansoni

Infected mother rats, resistant to Schistosoma mansoni, yielded offspring that were significantly resistant to a primary infection with cercariae, demonstrating the maternal transfer of protection. Newborns of normal mother rats could also be made resistant by the injection of protective immune rat serum, indicating that the effector phase components required for expression of protective activity are present in the newborn rat. The injection of the protective antiserum into newborns of the infected mothers enhanced resistance to a level exceeding 90%.     

Dissecting the dynamics of trans‐generational immune priming

The transfer of immunity from mother to offspring is a central way to endow the offspring with increased protection against pathogens. This phenomenon is not only found within the vertebrate domain: in some circumstances, invertebrate mothers can also give their offspring an immune kick‐start, which is termed trans‐generational immune priming (TGIP). TGIP has been uncovered for a number of invertebrate species, but it is not ubiquitously evident. The reasons for which are not known. In this issue of Molecular Ecology, Tate, Andolfatto, Demuth, and Graham ( 2017 ) probe the molecular underpinnings of TGIP in concert with the temporal dynamics of the response in the red flour beetle, Tribolium castaneum, infected with the bacterium Bacillus thuringiensis (Figure  1 ). They provide previously lacking evidence for the repeatability of TGIP, meaning that when averaged across several experiments, the offspring of mothers infected with heat‐killed bacteria had better survival when they themselves were infected with live bacteria than offspring from mothers that had not encountered the bacterium. In a detailed temporal examination of the offspring's acute infection phase (zero to 24 hr after infection), Tate et al. ( 2017 ) follow T. castaneum's gene regulation responses to infection while simultaneously documenting bacterial load. Such an approach gives considerable insight into the physiological processes that occur in primed offspring, and a first glance at a potential role for tolerance and effects on host metabolism that might even resemble trained immunity, which is a form of innate immune memory in vertebrates.     

Transgenerational priming of immunity: maternal exposure to a bacterial antigen enhances offspring humoral immunity

Young vertebrates have limited capacity to synthesize antibodies and are dependent on the protection of maternally transmitted antibodies for humoral disease resistance early in life. However, mothers may enhance fitness by priming their offspring's immune systems to elevate disease resistance. Transgenerational induced defences have been documented in plants and invertebrates, but maternal priming of offspring immunity in vertebrates has been essentially neglected. To test the ability of mothers to stimulate the immune systems of offspring, we manipulated maternal and offspring antigen exposure in a wild population of birds, pied flycatchers (Ficedula hypoleuca). We show that immunization of the mother before egg laying apparently stimulates a transgenerational defence against pathogens by elevating endogenous offspring antibody production. If the disease environments encountered by mothers and offspring are similar, this transgenerational immune priming may allow young to better cope with the local pathogen fauna.     

Maternal transfer of antibodies in vertebrates: trans-generational effects on offspring immunity

Maternal effects by which females provide their offspring with non-genetic factors such as hormones, nutrients and antibodies can have an important impact on offspring fitness. In vertebrates, maternal antibodies (matAb) are transferred from the mother, via the placenta, egg yolk or milk during lactation to offspring until they are 2 weeks (birds), 4-10 weeks (rodents) and 9 months (humans) old, respectively. matAb transfer can have direct effects on offspring growth rate in birds and rodents, probably by passively protecting the newborn from common pathogens before their endogenous immune system has matured. Indirect long-term effects of matAb transfer on the offspring's own immunity can be synergistic, if matAb act as antigen templates of the accumulated immunological experience of the mother and educate the newborn's immune system. However, it may also be suppressive if matAb reduce antigen presentation to the newborn resulting in antigen-specific blocking of offspring endogenous immunity. Our aim is to review the mechanisms and direct effects of matAb transfer in vertebrates with an emphasis on birds, outline a framework for research on the long-term effects of matAb on the endogenous immune system of the mature offspring and encourage ecological and evolutionary studies of matAb transfer in non-domesticated animals.     

Trans‐generational immune priming is constrained by the maternal immune response in an insect

Immune‐challenged vertebrate and invertebrate females can transfer immunity to their offspring. This trans‐generational immune priming (TGIP) is beneficial for the offspring if the maternal infection risk persists across generations. However, because immunity is costly, fitness consequences of TGIP have been found in primed offspring. Furthermore, transferring immunity to offspring may be costly for immune‐challenged females who are also carrying the costs of their immune response. A negative relationship between levels of immunity between mothers and offspring might therefore be expected. Consistent with this hypothesis, we show that in the insect, Tenebrio molitor, the magnitude of antibacterial immune response of immune‐challenged females negatively correlates with levels of antibacterial activity of their eggs. This negative relationship was only present in small females that are inherently of lower quality. Furthermore, female body size did not affect immune responsiveness to the challenge, indicating that small females favoured their immunity at the expenses of that of their eggs.     

Effects of perinatal exposure to Zamzam water on the teratological studies of the mice offspring

Zamzam water is well documented for plenty of medicinal value for curing illness. In the present study, the effects of perinatal consumption of Zamzam and normal drinking water by the pregnant mice on their offspring’s physical parameters, early sensory motor reflexes, locomotor activities, acetylcholinesterase (AChE) activity in the homogenize brain tissue and blood parameters were compared. To achieve that; Zamzam water was given to female Swiss-Webster strain mice as the only source of drinking fluid and the control animals were administered plain tap water. Treatment started from the first day of pregnancy and continued until the postnatal day fifteen of delivery. All offspring were subjected to various tests. The rate of body weight gain remained relatively unaffected until the second week of weaning period, however; in the last week the offspring exposed to Zamzam water gained significant body weight as compared to their control offspring. Furthermore, the opening of eyes and appearance of body hairs in Zamzam exposed pups remained unaffected as compared to the controls. The sensory motor reflexes in Zamzam exposed pups after birth and during the first two weeks of weaning period were significantly increased. Locomotor Activity Test performed in the male and female offspring after weaning period showed a significant decrease in the male and increase in the female on most of the elements of this test due to Zamzam exposure. AChE activity in the homogenized brain tissue and blood parameters were unaffected as compared to the controls, the present Zamzam effects in the offspring are possibly via in utero action and/or via mother’s milk.     

Maternal antibodies in a wild altricial bird: effects on offspring immunity, growth and survival

1. In many animals immunity is not fully developed until adulthood but the young still need protection against various sets of pathogens. Thus, bird nestlings are highly dependent on antibodies received from their mother (in the eggs) during their rapid early growth period. The relationship between maternal immunity and the development of neonates' own immunity has been poorly studied. 2. It has been suggested that immune function plays an important part in mediating resource competition between different life-history traits, e.g. growth and reproduction. Maternal investment of antibodies has potentially permanent effects on offspring phenotype. Thus, the trade-offs between the immune function and other important life-history traits in the offspring will also affect the fitness of the mother. 3. Our supplemental feeding experiment in the magpie Pica pica indicates that the immunoglobulin levels of offspring at hatching are dependent on a mother's nutritional condition. In addition, the amount of maternal immunoglobulins transferred to offspring increases along the laying order within a nest. 4. We also found that at the age of 8-10 days the immunoglobulin production of the offspring has already begun. Furthermore, the maternal immunoglobulin levels of the offspring at hatching were positively related to their immunoglobulin levels on day 10. 5. Maternal immunoglobulins did not significantly affect offspring growth, but there was a negative relationship between self-produced immunoglobulins and growth over the first 10 days, indicating a trade-off between these traits. Nestlings' weight, however, had a positive relationship with immunoglobulin production suggesting that the observed trade-off between growth and immunoglobulin production is due to catch-up growth of nestlings with a low hatching weight. We found that within nests nestlings with higher maternal antibody levels had higher survival rate until day 20, but between nests there was an opposite relationship. 6. Evidently, there is a trade-off, in magpies, between maternal resources, immune function and growth, shaping the evolution of maternal investment in offspring immunity.     

A distinct infection cost associated with trans-generational priming of antibacterial immunity in bumble-bees

The adaptive value of facultative maternal adjustment of offspring immunity, or trans-generational immune-priming, will depend on the ecological background. In particular, where there is a mismatch between the immune adjustment and offspring environment, the immunological link between mothers and offspring may be disadvantageous owing to the presence of associated costs. Costs to an individual of responding to an immune challenge are extensively documented. However, in addition to parents, the relevant costs for trans-generational immune-priming also pertain to offspring, but as yet it is unknown what costs offspring will bear. In bumble-bees, higher antibacterial activity has been shown as a trans-generational effect when mothers receive a bacterial-based immune challenge prior to colony founding. Here we show that while naive offspring from immune-challenged mothers do not show evidence for a direct energy-related survival cost, they do show increased susceptibility to a parasite distinctly unrelated to the maternal challenge. The presence of costs associated with trans-generational immune-priming will shape the evolution of this trait depending on the ecological setting.     

Obligate symbionts activate immune system development in the tsetse fly

Many insects rely on the presence of symbiotic bacteria for proper immune system function. However, the molecular mechanisms that underlie this phenomenon are poorly understood. Adult tsetse flies (Glossina spp.) house three symbiotic bacteria that are vertically transmitted from mother to offspring during this insect's unique viviparous mode of reproduction. Larval tsetse that undergo intrauterine development in the absence of their obligate mutualist, Wigglesworthia, exhibit a compromised immune system during adulthood. In this study, we characterize the immune phenotype of tsetse that develop in the absence of all of their endogenous symbiotic microbes. Aposymbiotic tsetse (Glossina morsitans morsitans [Gmm(Apo)]) present a severely compromised immune system that is characterized by the absence of phagocytic hemocytes and atypical expression of immunity-related genes. Correspondingly, these flies quickly succumb to infection with normally nonpathogenic Escherichia coli. The susceptible phenotype exhibited by Gmm(Apo) adults can be reversed when they receive hemocytes transplanted from wild-type donor flies prior to infection. Furthermore, the process of immune system development can be restored in intrauterine Gmm(Apo) larvae when their mothers are fed a diet supplemented with Wigglesworthia cell extracts. Our finding that molecular components of Wigglesworthia exhibit immunostimulatory activity within tsetse is representative of a novel evolutionary adaptation that steadfastly links an obligate symbiont with its host.     

Transgenerational effect of infection in Plasmodium-infected mosquitoes

Transgenerational effects of infection have a huge potential to influence the prevalence and intensity of infections in vectors and, by extension, disease epidemiology. These transgenerational effects may increase the fitness of offspring through the transfer of protective immune factors. Alternatively, however, infected mothers may transfer the costs of infection to their offspring. Although transgenerational immune protection has been described in a dozen invertebrate species, we still lack a complete picture of the incidence and importance of transgenerational effects of infection in most invertebrate groups. The existence of transgenerational infection effects in mosquito vectors is of particular interest because of their potential for influencing parasite prevalence and intensity and, by extension, disease transmission. Here we present what we believe to be the first study on transgenerational infection effects in a mosquito vector infected with malaria parasites. The aim of this experiment was to quantify both the benefits and the costs of having an infected mother. We find no evidence of transgenerational protection in response to a Plasmodium infection. Having an infected mother does, however, entail considerable fecundity costs for the offspring: fecundity loss is three times higher in infected offspring issued from infected mothers than in infected offspring issued from uninfected mothers. We discuss the implications of our results and we call for more studies looking at transgenerational effects of infection in disease vectors.     

Maternal infection: window on neuroimmune interactions in fetal brain development and mental illness

Direct viral infection of the developing brain can have disastrous consequences for the fetus. More subtle and perhaps more insidious are viral infections of the pregnant mother, which can have long-lasting effects such as an increased risk of schizophrenia in the offspring. A recent mouse model has shown that respiratory infection in the pregnant mother leads to marked behavioral and pharmacological abnormalities in the offspring, some of which are relevant for schizophrenia and autism. This effect on fetal brain development might be caused by the maternal antiviral immune response, possibly mediated by cytokines.     

Relationship between maternal transfer of immunity and mother fecundity in an insect

Trans-generational immune priming (TGIP) corresponds to the plastic adjustment of offspring immunity as a result of maternal immune experience. TGIP is expected to improve mother's fitness by improving offspring individual performance in an environment where parasitism becomes more prevalent. However, it was recently demonstrated that maternal transfer of immunity to the offspring is costly for immune-challenged female insects. Thus, these females might not provide immune protection to all their offspring because of the inherent cost of other fitness-related traits. Females are therefore expected to adjust their investment to individual offspring immune protection in ways that maximize their fitness. In this study, we investigated how bacterially immune-challenged females of the mealworm beetle, Tenebrio molitor, provision their eggs with immune protection according to egg production. We found that immune-challenged females provide a variable number of their eggs with internal antibacterial activity along egg-laying bouts. Furthermore, within the first immune-protected egg-laying bout (2-4 days after the maternal immune challenge), the number of eggs protected was strongly dependent on the number of eggs produced. Immune-challenged females might therefore adjust their investment into TGIP and fecundity according of their individual perception of the risk of dying from the infection and the expected parasitic conditions for the offspring.     

Hyperglycaemia in pregnancy: effects on the offspring behaviour with special reference to anxiety paradigms

Maternal hyperglycemic effect was studied on the offspring behaviour. Offspring were obtained from diabetic rats by mating a normal father with a diabetic mother (NFDM), diabetic father with normal mother (DFNM) and diabetic father with diabetic mother (DFDM). Rats were rendered diabetic by injecting streptozotocin (STZ, 50 mg/kg i.p.) in citrate buffer. Offspring were subjected to various anxiety parameters including open field exploratory behaviour, elevated plus maze and zero maze behaviours, and the social interaction tests at the age of 8 weeks. The results indicate that offspring of NFDM and DFDM showed anxiogenic activity on the elevated plus maze zero maze and the social interaction test. Offspring of NFDM and DFDM exhibited hyper and emotional activity in the open field behaviour test. The behavioural alterations observed in the offspring were comparable to the behavioural alterations noted in STZ diabetic rat as reported earlier. Further offspring of NFDM and DFDM exhibited mild hyperglycaemia. No significant behavioural alterations in the offspring of DFNM were observed. It may be concluded, that exposure of offspring to diabetic environment in their foetal life can lead to anxiogenic/emotional behaviours in adult life.     

Gender-Dependent Effects of Maternal Immune Activation on the Behavior of Mouse Offspring

Autism spectrum disorders are neurodevelopmental disorders characterized by two core symptoms; impaired social interactions and communication, and ritualistic or repetitive behaviors. Both epidemiological and biochemical evidence suggests that a subpopulation of autistics may be linked to immune perturbations that occurred during fetal development. These findings have given rise to an animal model, called the “maternal immune activation” model, whereby the offspring from female rodents who were subjected to an immune stimulus during early or mid-pregnancy are studied. Here, C57BL/6 mouse dams were treated mid-gestation with saline, lipopolysaccharide (LPS) to mimic a bacterial infection, or polyinosinic:polycytidylic acid (Poly IC) to mimic a viral infection. Autism-associated behaviors were examined in the adult offspring of the treated dams. Behavioral tests were conducted to assess motor activity, exploration in a novel environment, sociability, and repetitive behaviors, and data analyses were carried independently on male and female mice. We observed a main treatment effect whereby male offspring from Poly IC-treated dams showed reduced motor activity. In the marble burying test of repetitive behavior, male offspring but not female offspring from both LPS and Poly IC-treated mothers showed increased marble burying. Our findings indicate that offspring from mothers subjected to immune stimulation during gestation show a gender-specific increase in stereotyped repetitive behavior.