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Behavioral biology of Toxoplasma gondii infection
Parasites & Vectors volume 14, Article number: 77 (2021)
Toxoplasma gondii is a protozoan parasite with a complex life cycle and a cosmopolitan host range. The asexual part of its life cycle can be perpetually sustained in a variety of intermediate hosts through a combination of carnivory and vertical transmission. However, T. gondii produces gametes only in felids after the predation of infected intermediate hosts. The parasite changes the behavior of its intermediate hosts by reducing their innate fear to cat odors and thereby plausibly increasing the probability that the definitive host will devour the infected host. Here, we provide a short description of such parasitic behavioral manipulation in laboratory rodents infected with T. gondii, along with a bird’s eye view of underpinning biological changes in the host. We also summarize critical gaps and opportunities for future research in this exciting research area with broad implications in the transdisciplinary study of host–parasite relationships.
What is Toxoplasma gondii?
Toxoplasma gondii is an enteric coccidian parasite of the cat. As an apicomplexan protist, T. gondii is an intracellular parasite that completes its life cycle within the small intestine of the cat, which is the definitive host, where the parasite undergoes sexual reproduction to produce oocysts. These unsporulated oocysts, which measure 11–13 μm in diameter, are excreted in the infected cat’s feces. Following development in the environment, termed sporulation, the sporulated oocysts that are ingested by an intermediate host release sporozoites, and these infect the cells of the intestine and lymph nodes where they transform into a rapidly dividing asexual stage termed a tachyzoite. The tachyzoites disseminate to other parts of the body, and their rapid multiplication and associated destruction of host cells result in acute toxoplasmosis, which is characterized by mild to severe clinical signs depending on the organ system affected and the immune status of the host. Following this acute stage, the formation of tissue cysts containing a slow reproducing bradyzoite stage occurs. These tissue cysts, which typically form in the brain, liver and muscle, can persist for the life of the intermediate host. Upon ingestion by the cat, bradyzoites are released from tissue cysts and undergo asexual reproduction within the epithelium of the cat small intestine, followed by sexual reproduction and the production of oocysts. However, if other intermediate hosts ingest the tissue cysts, the acute stage of the life cycle, characterized by tachyzoite replication and dissemination, is initiated. If infection occurs during pregnancy, tachyzoites can be transmitted vertically to the fetus. They may be associated with severe clinical outcomes depending on the timing of the infection and the host species involved.
Toxoplasma gondii is considered to be one of the most “successful” parasites since virtually any warm-blooded animal can serve as a paratenic host. In humans, exposure is frequent, with estimated exposure rates of between 30 and 35% in the general population . However, exposure rates are significantly influenced by dietary habits and behavior and can range from 10 to 80% in specific populations [2, 3].
Effects on host behavior
If a laboratory-reared rat is placed in a box with a few drops of cat urine in one corner it will avoid the corner with the cat urine. The rat will also secrete stress hormones, increase vigilance, and be less likely to feel pain. Rats have an innate fear of cues of cats being nearby. Now, if a rat similar in all aspects with the first rat with the exception it has been previously infected with T. gondii is placed in the same box, this infected rat does not avoid the corner with the urine [4, 5]. Some infected rats are even attracted to the odor. In other words, T. gondii removes the innate fear of rats and converts it, in at least some individuals, into attraction, a feat which decades of laboratory-rearing sans-predator has not yet achieved. Why does it happen? The most popular explanation is that a fearless rat is more likely to be eaten by a cat, which is beneficial for T. gondii because it forms gametes in the cat, the definitive host, and is then excreted in the feces in the form of environmentally stable oocysts. Thus, T. gondii manipulates the behavior of its host to increase its transmission. The rodent–T. gondii model is, in fact, one of the most studied models of parasitic behavioral manipulation [6,7,8,9,10,11,12].
However, there is a wide range of views on just how specific the behavioral effects of T. gondii infection are. These can be broadly classified into three views. First, a set of studies suggest that T. gondii effects are rather specific to the avoidance of cat odors, with odors of non-predators, or predators not important for the parasite’s life cycle being less influenced by the manipulative effects of the parasite [5, 13]. A second set of studies reports that the effects are syndromic, in that infection causes a loss of a suite of host defensive behaviors. Thus, trappability increases even if human-made traps are not similar to cats. Infected rats become more exploratory, more open to taking risks and become altogether more impulsive [14,15,16,17,18,19,20,21]. Finally, a third set of studies suggests that T. gondii causes something akin to a behavioral fever that includes a broad range of behavioral changes that are ill-suited for the host, and that the combination of these changes might increase predation by cats [22,23,24,25,26,27,28,29]. Why is there such a diversity of notions? A large part of this diversity comes from the specific strains of T. gondii and rodent species being used the study. The majority of genetic diversity found in T. gondii can be found in three clonal lineages . Of these, infection of rats with the less virulent type II strains typically leads to smaller magnitude of sickness behaviors during the acute phase of the infection. These infections, in turn, cause more specific behavioral effects during the chronic period. Accordingly, T. gondii infection of outbred rats or infection with low-virulence parasites produce remarkably specific behavioral effects with minimal sickness behavior [4, 5, 31]. On the other hand, infection of inbred mice with virulent type I parasite strains causes much acute sickness and less specific behavioral effects [22, 28, 32, 33]. Thus, the behavioral outcome of T. gondii infection systematically varies with the host–parasite strain combinations.
Why study the behavioral biology of T. gondii?
Biologists have been long interested in the relationship between parasitism and host behavior. Continual coevolution with parasites, for example, has been used to explain the persistence of heritable sexual advertisements in males . Similarly, the concept of extended phenotypes often uses behavioral manipulation of the host by parasites as a rhetoric device to argue that natural selection acts on genetic information and not on individuals . Several parasites change the behavior of their hosts, presumably to increase the transmission efficiency. Thus, genes of parasites can cause a phenotype outside of the physical confines of the individual body of the parasite; for that reason, selection operates on the genetic information of the parasite rather than on its physical individuality. T. gondii infection of laboratory rodents provides an experimentally tractable system in which testable hypotheses about extended phenotypes can be examined.
Also, behavioral neurobiologists can use T. gondii as a perturbation model to understand innate fear in much the same way as a geneticist might use naturally occurring allelic mutation. This is a critical pursuit because the biology of fear relates to the biology of psychiatric diseases, such as posttraumatic stress disorder. Studies on T. gondii behavioral biology have led to several exciting discoveries in neuroendocrinology, including the organization of brain–hormone communication (e.g. ).
Medical research on T. gondii was once restricted to immune-compromised patients. However, the discovery of behavioral changes in T. gondii-infected humans has slowly revised that focus. Concordance studies show that T. gondii increases the odds of developing psychiatric disorders such as schizophrenia, bipolar disorder and obsessive-compulsive disorder [37, 38]. These retrospective estimates have been confirmed by prospective studies in the case of schizophrenia [39, 40] (but see lack of evidence in a birth cohort study ). Multiple case–control studies also show that latent T. gondii infection is associated with systematic changes in human personality [42, 43], ranging from risk-taking to entrepreneurship [44, 45].
Manipulative parasites represent an exciting gap in the study of ecological systems . For example, prey–predator interactions can often lead to trophic cascades, indirect effects that percolate to resources consumed by the prey. Manipulative parasites like T. gondii are likely to affect such cascades due to the creation of heterogeneity in the probability of consumption of infected versus non-infected prey. Similarly, the specificity of T. gondii behavior effects, specifically definitive versus dead-end host, might influence prey switching by generalist predators like raptors and owls .
Toxoplasma gondii and its attendant effects of host behavior thus provide a unique transdisciplinary intersection between diverse fundamental and applied biological disciplines.
Three advances in T. gondii behavioral biology
Toxoplasma gondii infection alters host hormones
Toxoplasma gondii exhibits a decided tropism for the brain and eyes. These organs are immune privileged in that they afford limited access to immune cells. Interestingly, the brain and eyes are not the only immune-privileged sites in the mammalian body. Male testes segregate developing sperms behind a tight barrier that largely excludes the entry of immune cells. Very few pathogens succeed in crossing the blood–testes barrier; yet T. gondii does cross this barrier and invades testes in rats . Accordingly, T. gondii is found in the ejaculates of rats and several other species [48,49,50,51,52] (but not in mice ). Moreover, T. gondii increases the synthesis of testosterone , a testicular hormone that reduces fear and anxiety . The extra testosterone is crucial for T. gondii effects, primarily through its interaction with the brain. Castration prevents behavioral change, and T. gondii-like effects can be recapitulated by the infusion of testosterone within the host brain . This raises an obvious but unanswered question: how does T. gondii change the behavior of testes-free females ?
Toxoplasma gondii infection alters neurotransmission within the host brain
Chronic T. gondii infection causes specific changes in chemical messengers used by inter-neuronal connections within the brain. The T. gondii genome contains two loci with high homology for mammalian genes coding for a rate-limiting enzyme in dopamine synthesis, namely amino acid hydroxylase . This homology suggests that T. gondii, once resident within the brain, can increase the availability of dopamine [57, 58], a neurotransmitter critical for the processing of motivation and pleasure. Interestingly, drugs that interfere with dopamine metabolism also rescue the effects of T. gondii on behavior . Nonetheless, genetic ablation of at least one of these genes does not rescue T. gondii-induced behavioral manipulation [60, 61]. Toxoplasma gondii infection also increases the synthesis of arginine vasopressin in a specific brain region called the medial amygdala . These neurons are involved in the perception of sexual pheromone and connected to brain regions involved in motivation . One proposal is, therefore, that the extra dopamine or arginine vasopressin or both cause animals to become impulsive and reckless, leading to a reduction in fear.
Toxoplasma gondii effects could be mediated through neuroinflammation
The host immune system is critical in limiting the acute phase of T. gondii infection and then maintaining encystment during repeated cycles of recrudescence. Results from several studies suggest that inflammation also plays an essential role in mediating behavioral effects. For example, the number of cysts in the mouse brain and its attendant immune response correlates with the magnitude of behavioral change . Similarly, an anti-inflammatory drug, guanabenz, reduces the behavioral effects of the infection . The authors of these studies argue that the behavioral manipulation is not as specific to cat odors as initially suggested, but is instead part of a multi-faceted alteration caused by the continual immune challenge. Yet, T. gondii strains that do not cause sustained encystment in the mouse brain still able to manipulate behavior . Moreover, it is possible to rescue behavioral effects by blocking molecular changes within restricted brain regions, a treatment unlikely to affect cyst density . Specific versus aspecific effects of T. gondii likely reflect molecular traits specific to the host species.
Three opportune research areas
Consequences of the infection on predation rates
The central theme of the behavioral manipulation hypothesis is that parasites can change host behavior and that this change has a current adaptive value for the parasite. While there are several examples of host behavioral change , the adaptive value for the parasites remains unquantified in the vast majority of these cases. Apropos, it is unknown if T. gondii increases predation rates of the infected rodents by cats, and if the possible facilitation generalizes to non-cat predators, such as birds of prey. Toxoplasma gondii can perpetually maintain the asexual phase of its life cycle without cats , while gametogenesis requires cats, although genetic heterogeneity of the parasite and benefits reaped by recombination remain doubtful. Nonetheless, cats provide an opportunity to infect herbivores as well as the host for the generation of copious amounts of environmentally resistant oocysts. In terms of behavioral facilitation of predation, therefore, it is critical to understand both the behavioral manipulation hypothesis and the relative strengths of the transmission modes. In this context, it is crucial to ascertain whether T. gondii-infected rodents are consumed at a higher rate by cats than non-infected individuals.
Consequences of the infection for life-history plasticity
An increase in parasite-mediated predation can have important implications for host life-history traits, including the relative balance between current and residual reproduction. Animals respond to increased risk of death by creating myopic life histories that favor earlier reproduction even if this is a trade-off with survival . For example, Tasmanian devils reproduce earlier in response to facial tumor disease as the probability of being alive during second or third episodes of reproduction becomes constrained . If T. gondii increases predation rates, then it is likely that the host will respond with abbreviated life histories. Such adjustments will alter ecological interactions at the community level and reconfigure the flow of energy through trophic levels. Thus, the critical unanswered questions include: does T. gondii alter life-history traits; does such change reflect phenotypic plasticity or genetic heterogeneity within hosts; and do these non-consumptive changes in the host percolate through ecological communities? Focusing on answering such questions is also an opportunity to understand the theoretical relationships between the effects of parasitism and non-parasitic clinical conditions .
Making sense of diverse host–parasite combinations
Experiments show a large variability in behavioral effects of T. gondii, especially between studies using rats and mice. It remains unknown if this variability reflects a genetic divergence in species or represents a result of recent inbreeding in laboratory strains. Behavioral studies using other hosts are rare to find. This gap is a significant research opportunity to build phylogenetic comparisons of behavioral responses to the infection. There is a need to demonstrate convergence and divergence across phylogenetic branches in order to demonstrate the historical processes of selection on the parasite. Such systematic comparisons are also crucial to improving our understanding of the implications of parasitism on the evolution of host behavior, for example, to answer if manipulative and non-manipulative parasites provide different pressures on host sexual selection. The differential effects of T. gondii strains on host behavior are another provocative area of research in which the use of genetic crosses of the parasite may help to map relevant loci in the parasite genome.
More than five decades ago, Niko Tinbergen articulated four crucial vantage points to understanding behavior : mechanisms, development, current adaptive value and evolutionary origin. This framework has often been used as a scaffold on which to organize scientific knowledge in behavior and associated disciplines . The same structure can serve well to organize current advances and areas ripe for future research on T. gondii behavioral biology. Starting from a careful demonstration of parasitic host behavioral change, the model has slowly dovetailed into detailed experiments about the mechanisms, the first player in Tinbergen’s quartet. We have not yet identified the T. gondii genes or effector proteins responsible for parasitic behavioral change. Nevertheless, considerable progress has been made in the domain of downstream neuroendocrine changes within the host. The other three players in Tinbergen’s quartet, namely developmental plasticity, adaptive value and evolutionary origins, remain unexplored areas ripe for future investigation. Parasites are robust drivers of host behavior, with cardinal influences in anti-predator defense and sexually selected traits. Hence, the elucidation of T. gondii behavioral biology has broad implications in the fields of neurobiology, behavioral ecology and evolutionary biology. This research enterprise is likely to see much scientific attention in the future.
A downloadable poster describing the behavioral biology of T. gondii is available in Additional file 1: Poster S1.
Availability of data and materials
Robert-Gangneux F, Dardé M-L. Epidemiology of and diagnostic strategies for toxoplasmosis. Clin Microbiol Rev. 2012;25:264–96.
Flegr J, Prandota J, Sovičková M, Israili ZH. Toxoplasmosis—a global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries. PLoS ONE. 2014;9:e90203.
Jones JL, Parise ME, Fiore AE. Neglected parasitic infections in the United States: toxoplasmosis. Am J Trop Med Hyg. 2014;90:794–9.
Berdoy M, Webster JP, Macdonald DW. Fatal attraction in rats infected with Toxoplasma gondii. Proc Biol Sci. 2000;267:1591–4.
Vyas A, Kim SK, Giacomini N, Boothroyd JC, Sapolsky RM. Behavioral changes induced by Toxoplasma infection of rodents are highly specific to aversion of cat odors. Proc Natl Acad Sci USA. 2007;104:6442–7.
Tyebji S, Seizova S, Hannan AJ, Tonkin CJ. Toxoplasmosis: a pathway to neuropsychiatric disorders. Neurosci Biobehav Rev. 2019;96:72–92.
Johnson HJ, Koshy AA. Latent toxoplasmosis effects on rodents and humans: how much is real and how much is media hype? mBio. 2020;11:e02164-e2219.
Lafferty KD. Look what the cat dragged in: do parasites contribute to human cultural diversity? Behav Processes. 2005;68:279–82.
McConkey GA, Martin HL, Bristow GC, Webster JP. Toxoplasma gondii infection and behaviour—location, location, location? J Exp Biol. 2013;216:113–9.
Vyas A. Mechanisms of host behavioral change in Toxoplasma gondii rodent association. PLoS Pathog. 2015;11:e1004935.
Webster JP, McConkey GA. Toxoplasma gondii-altered host behaviour: clues as to mechanism of action. Folia Parasitol (Praha). 2010;57:95–104.
Worth AR, Andrew Thompson RC, Lymbery AJ. Reevaluating the evidence for Toxoplasma gondii-induced behavioural changes in rodents. Adv Parasitol. 2014;85:109–42.
Lamberton PH, Donnelly CA, Webster JP. Specificity of the Toxoplasma gondii-altered behaviour to definitive versus non-definitive host predation risk. Parasitology. 2008;135:1143–50.
Berdoy M, Webster JP, Macdonald DW. Parasite-altered behaviour: is the effect of Toxoplasma gondii on Rattus norvegicus specific? Parasitology. 1995;111(Pt 4):403–9.
Tan D, Soh LJ, Lim LW, Daniel TC, Zhang X, Vyas A. Infection of male rats with Toxoplasma gondii results in enhanced delay aversion and neural changes in the nucleus accumbens core. Proc Biol Sci. 2015;282:20150042.
Tan D, Vyas A. Toxoplasma gondii infection and testosterone congruently increase tolerance of male rats for risk of reward forfeiture. Horm Behav. 2016;79:37–44.
Tan D, Vyas A. Infection of male rats with Toxoplasma gondii induces effort-aversion in a T-maze decision-making task. Brain Behav Immun. 2016;53:273–7.
Vyas A, Kim SK, Sapolsky RM. The effects of Toxoplasma infection on rodent behavior are dependent on dose of the stimulus. Neuroscience. 2007;148:342–8.
Webster JP. The effect of Toxoplasma gondii and other parasites on activity levels in wild and hybrid Rattus norvegicus. Parasitology. 1994;109(Pt 5):583–9.
Webster JP, Brunton CF, MacDonald DW. Effect of Toxoplasma gondii upon neophobic behaviour in wild brown rats Rattus norvegicus. Parasitology. 1994;109(Pt 1):37–43.
Afonso C, Paixão VB, Costa RM. Chronic Toxoplasma infection modifies the structure and the risk of host behavior. PLoS ONE. 2012;7:e32489.
Boillat M, Hammoudi PM, Dogga SK, Pagès S, Goubran M, Rodriguez I, et al. Neuroinflammation-associated aspecific manipulation of mouse predator fear by Toxoplasma gondii. Cell Rep. 2020;30(320–34):e6.
Eells JB, Varela-Stokes A, Guo-Ross SX, Kummari E, Smith HM, Cox E, et al. Chronic Toxoplasma gondii in Nurr1-null heterozygous mice exacerbates elevated open field activity. PLoS One. 2015;10:e0119280.
Gulinello M, Acquarone M, Kim JH, Spray DC, Barbosa HS, Sellers R, et al. Acquired infection with Toxoplasma gondii in adult mice results in sensorimotor deficits but normal cognitive behavior despite widespread brain pathology. Microbes Infect. 2010;12:528–37.
Ihara F, Nishimura M, Muroi Y, Mahmoud ME, Yokoyama N, Nagamune K, et al. Toxoplasma gondii infection in mice impairs long-term fear memory consolidation through dysfunction of the cortex and amygdala. Infect Immun. 2016;84:2861–70.
Mahmoud ME, Fereig R, Nishikawa Y. Involvement of host defense mechanisms against Toxoplasma gondii Infection in anhedonic and despair-like behaviors in mice. Infect Immun. 2017;85:e00007-17.
Mahmoud ME, Ihara F, Fereig RM, Nishimura M, Nishikawa Y. Induction of depression-related behaviors by reactivation of chronic Toxoplasma gondii infection in mice. Behav Brain Res. 2016;298:125–33.
Tyebji S, Hannan AJ, Tonkin CJ. Pathogenic infection in male mice changes sperm small RNA profiles and transgenerationally alters offspring behavior. Cell Rep. 2020;31:107573.
Xiao J, Li Y, Prandovszky E, Kannan G, Viscidi RP, Pletnikov MV, et al. Behavioral abnormalities in a mouse model of chronic toxoplasmosis are associated with MAG1 antibody levels and cyst burden. PLoS Negl Trop Dis. 2016;10:e0004674.
Saeij JP, Boyle JP, Boothroyd JC. Differences among the three major strains of Toxoplasma gondii and their specific interactions with the infected host. Trends Parasitol. 2005;21:476–81.
Ingram WM, Goodrich LM, Robey EA, Eisen MB. Mice infected with low-virulence strains of Toxoplasma gondii lose their innate aversion to cat urine, even after extensive parasite clearance. PLoS One. 2013;8:e75246.
Soh LJ, Vasudevan A, Vyas A. Infection with Toxoplasma gondii does not elicit predator aversion in male mice nor increase their attractiveness in terms of mate choice. Parasitol Res. 2013;112:3373–8.
Hodkova H, Kodym P, Flegr J. Poorer results of mice with latent toxoplasmosis in learning tests: impaired learning processes or the novelty discrimination mechanism? Parasitology. 2007;134:1329–37.
Hamilton WD, Zuk M. Heritable true fitness and bright birds: a role for parasites? Science. 1982;218:384–7.
Dawkins R. The extended phenotype, vol. 8. Oxford: Oxford University Press; 1982.
Tong WH, Abdulai-Saiku S, Vyas A. Medial amygdala arginine vasopressin neurons regulate innate aversion to cat odors in male mice. Neuroendocrinology. 2021;111:505–20.
Sutterland AL, Fond G, Kuin A, Koeter MW, Lutter R, Van Gool T, et al. Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis. Acta Psychiatr Scand. 2015;132:161–79.
Xiao J, Prandovszky E, Kannan G, Pletnikov MV, Dickerson F, Severance EG, et al. Toxoplasma gondii: biological parameters of the connection to schizophrenia. Schizophr Bull. 2018;44:983–92.
Hinze-Selch D, Däubener W, Eggert L, Erdag S, Stoltenberg R, Wilms S. A controlled prospective study of Toxoplasma gondii infection in individuals with schizophrenia: beyond seroprevalence. Schizophr Bull. 2007;33:782–8.
Pedersen MG, Stevens H, Pedersen CB, Nørgaard-Pedersen B, Mortensen PB. Toxoplasma infection and later development of schizophrenia in mothers. Am J Psychiatry. 2011;168:814–21.
Sugden K, Moffitt TE, Pinto L, Poulton R, Williams BS, Caspi A. Is Toxoplasma Gondii infection related to brain and behavior impairments in humans? Evidence from a population-representative birth cohort. PLoS One. 2016;11:e0148435.
Flegr J, Horáček J. Negative effects of latent toxoplasmosis on mental health. Front Psychiatry. 2019;10:1012.
Flegr J. How and why Toxoplasma makes us crazy. Trends Parasitol. 2013;29:156–63.
Johnson SK, Fitza MA, Lerner DA, Calhoun DM, Beldon MA, Chan ET, et al. Risky business: linking Toxoplasma gondii infection and entrepreneurship behaviours across individuals and countries. Proc Biol Sci. 2018;285:20180822.
Flegr J, Klose J, Novotná M, Berenreitterová M, Havlícek J. Increased incidence of traffic accidents in Toxoplasma-infected military drivers and protective effect RhD molecule revealed by a large-scale prospective cohort study. BMC Infect Dis. 2009;9:72.
Buck JC, Ripple WJ. Infectious agents trigger trophic cascades. Trends Ecol Evol. 2017;32:681–94.
Wilson AG, Lapen DR, Mitchell GW, Provencher JF, Wilson S. Interaction of diet and habitat predicts Toxoplasma gondii infection rates in wild birds at a global scale. Glob Ecol Biogeogr. 2020;29:1189–98.
Dass SA, Vasudevan A, Dutta D, Soh LJ, Sapolsky RM, Vyas A. Protozoan parasite Toxoplasma gondii manipulates mate choice in rats by enhancing attractiveness of males. PLoS One. 2011;6:e27229.
Lopes WD, da Costa AJ, Santana LF, Dos Santos RS, Rossanese WM, Lopes WC, et al. Aspects of Toxoplasma infection on the reproductive system of experimentally infected rams (ovis aries). J Parasitol Res. 2009;2009:602803.
Santana LF, da Costa AJ, Pieroni J, Lopes WD, Santos RS, de Oliveira GP, et al. Detection of Toxoplasma gondii in the reproductive system of male goats. Rev Bras Parasitol Vet. 2010;19:179–82.
Arantes TP, Lopes WD, Ferreira RM, Pieroni JS, Pinto VM, Sakamoto CA, et al. Toxoplasma gondii: evidence for the transmission by semen in dogs. Exp Parasitol. 2009;123:190–4.
Liu SG, Qin C, Yao ZJ, Wang D. Study on the transmission of Toxoplasma gondii by semen in rabbits. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2006;24:166–70.
Lim A, Kumar V, Hari Dass SA, Vyas A. Toxoplasma gondii infection enhances testicular steroidogenesis in rats. Mol Ecol. 2013;22:102–10.
Tong WH, Abdulai-Saiku S, Vyas A. Testosterone reduces fear and causes drastic hypomethylation of arginine vasopressin promoter in medial extended amygdala of male mice. Front Behav Neurosci. 2019;13:33.
Abdulai-Saiku S, Vyas A. Loss of predator aversion in female rats after Toxoplasma gondii infection is not dependent on ovarian steroids. Brain Behav Immun. 2017;65:95–8.
Gaskell EA, Smith JE, Pinney JW, Westhead DR, McConkey GA. A unique dual activity amino acid hydroxylase in Toxoplasma gondii. PLoS One. 2009;4:e4801.
Martin HL, Alsaady I, Howell G, Prandovszky E, Peers C, Robinson P, et al. Effect of parasitic infection on dopamine biosynthesis in dopaminergic cells. Neuroscience. 2015;306:50–62.
Prandovszky E, Gaskell E, Martin H, Dubey JP, Webster JP, McConkey GA. The neurotropic parasite Toxoplasma gondii increases dopamine metabolism. PLoS One. 2011;6:e23866.
Webster JP, Lamberton PH, Donnelly CA, Torrey EF. Parasites as causative agents of human affective disorders? The impact of anti-psychotic, mood-stabilizer and anti-parasite medication on Toxoplasma gondii’s ability to alter host behaviour. Proc Biol Sci. 2006;273:1023–30.
McFarland R, Wang ZT, Jouroukhin Y, Li Y, Mychko O, Coppens I, et al. AAH2 gene is not required for dopamine-dependent neurochemical and behavioral abnormalities produced by Toxoplasma infection in mouse. Behav Brain Res. 2018;347:193–200.
Wang ZT, Harmon S, O’Malley KL, Sibley LD. Reassessment of the role of aromatic amino acid hydroxylases and the effect of infection by Toxoplasma gondii on host dopamine. Infect Immun. 2015;83:1039–47.
Hari Dass SA, Vyas A. Toxoplasma gondii infection reduces predator aversion in rats through epigenetic modulation in the host medial amygdala. Mol Ecol. 2014;23:6114–22.
Martynowicz J, Augusto L, Wek RC, Boehm SL 2nd, Sullivan WJ Jr. Guanabenz reverses a key behavioral change caused by latent toxoplasmosis in mice by reducing neuroinflammation. mBio. 2019;10:e00381-e419.
Hughes DP, Brodeur J, Thomas F. Host manipulation by parasites. Oxford: Oxford University Press; 2012.
Dubey JP. Advances in the life cycle of Toxoplasma gondii. Int J Parasitol. 1998;28:1019–24.
Michalakis Y, Hochberg ME. Parasitic effects on host life-history traits: a review of recent studies. Parasite. 1994;1:291–4.
Jones ME, Cockburn A, Hamede R, Hawkins C, Hesterman H, Lachish S, et al. Life-history change in disease-ravaged Tasmanian devil populations. Proc Natl Acad Sci USA. 2008;105:10023–7.
Ujvari B, Beckmann C, Biro PA, Arnal A, Tasiemski A, Massol F, et al. Cancer and life-history traits: lessons from host–parasite interactions. Parasitology. 2016;143:533–41.
Tinbergen N. On aims and methods of ethology. Z tierpsychol. 1963;20:410–33.
Bateson P, Laland KN. Tinbergen’s four questions: an appreciation and an update. Trends Ecol Evol. 2013;28:712–8.
We thank Nanyang Technological University for the support in producing this manuscript.
This manuscript was supported by Human Frontier Science Program (RGP0062/2018). The funder had no role in the preparation of the manuscript. CP acknowledges support from the Alexander von Humboldt Foundation.
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Tong, W.H., Pavey, C., O’Handley, R. et al. Behavioral biology of Toxoplasma gondii infection. Parasites Vectors 14, 77 (2021). https://doi.org/10.1186/s13071-020-04528-x
- Behavioral manipulation
- Complex life cycle
- Extended phenotypes
- Parasitic manipulation