In vitro production of cat-restricted Toxoplasma pre-sexual stages.

Sexual reproduction of Toxoplasma gondii, confined to the felid gut, remains largely uncharted owing to ethical concerns regarding the use of cats as model organisms. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described1,2. Here we found that the transcription factors AP2XII-1 and AP2XI-2 operate during the tachyzoite stage, a hallmark of acute toxoplasmosis, to silence genes necessary for merozoites, a developmental stage critical for subsequent sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a marked change in the transcriptional program, promoting a full transition from tachyzoites to merozoites. These in vitro-cultured pre-gametes have unique protein markers and undergo typical asexual endopolygenic division cycles. In tachyzoites, AP2XII-1 and AP2XI-2 bind DNA as heterodimers at merozoite promoters and recruit MORC and HDAC3 (ref. 1), thereby limiting chromatin accessibility and transcription. Consequently, the commitment to merogony stems from a profound epigenetic rewiring orchestrated by AP2XII-1 and AP2XI-2. Successful production of merozoites in vitro paves the way for future studies on Toxoplasma sexual development without the need for cat infections and holds promise for the development of therapies to prevent parasite transmission.

Association between lymphadenopathy after toxoplasmosis seroconversion in pregnancy and risk of congenital infection.

The aim of the study was to describe the pregnancy outcome of a large cohort of women with toxoplasmosis seroconversion in pregnancy and to investigate the relation between maternal lymphadenopathy and risk of congenital toxoplasmosis (CT). This was a retrospective study involving women with confirmed toxoplasmosis seroconversion in pregnancy between 2001 and 2017. Women were clinically evaluated for lymphadenopathy and classified as follows: lymphadenopathy absent (L-) or lymphadenopathy present (L+). The mothers were treated and followed-up according to local protocol, and neonates were monitored at least for 1 year in order to diagnose CT. A total of 218 women (one twin pregnancy) were included in the analysis. Pregnancy outcome was as follows: 149 (68%) of children not infected, 62 (28.3%) infected, 4 (1.8%) first trimester termination of pregnancy, 2 (0.9%) first trimester miscarriages, and 3 (1.4%) stillbirths (of which one already counted in the infected cohort). 13.8% of women were L+ , and they were nearly three times more likely to have a child with CT compared to L- women (aOR, 2.90; 95%CI, 1.28-6.58). Moreover, the result was still statistically significant when the analysis was restricted to 81 children whose mothers were clinically examined and received treatment within 5 weeks from estimated time of infection. In conclusion, there is a positive association between L+ status in pregnant women, and risk of CT also confirmed when restricting the analysis to women with early diagnosis of seroconversion and treatment. This data could be very useful in counselling pregnant women with toxoplasmosis seroconversion and lead to direct a more specific therapeutic and diagnostic protocol.

The Role and Function of Regulatory T Cells in Toxoplasma gondii-Induced Adverse Pregnancy Outcomes.

Infection with Toxoplasma gondii (T. gondii) during the pregnant period and its potentially miserable outcomes for the fetus, newborn, and even adult offspring continuously occur worldwide. People acquire infection through the consumption of infected and undercooked meat or contaminated food or water. T. gondii infection in pregnant women primarily during the gestation causes microcephaly, mental and psychomotor retardation, or death. Abnormal pregnancy outcomes are mainly associated with regulatory T cell (Treg) dysfunction. Tregs, a special subpopulation of T cells, function as a vital regulator in maintaining immune homeostasis. Tregs exert a critical effect on forming and maintaining maternal-fetal tolerance and promoting fetal development during the pregnancy period. Forkhead box P3 (Foxp3), a significant functional factor of Tregs, determines the status of Tregs. In this review, we summarize the effects of T. gondii infection on host Tregs and its critical transcriptional factor, Foxp3.

A Novel Calcium-Dependent Protein Kinase 1 Inhibitor Potently Prevents Toxoplasma gondii Transmission to Foetuses in Mouse.

Treatments currently used to prevent congenital toxoplasmosis are non-specific of Toxoplasma gondii and have grievous side effects. To develop a more specific and less toxic drug, we have designed SP230, an imidazo[1,2-b]pyridazine salt targeting the Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) and active against acute toxoplasmosis in mice. Efficiency of SP230 to inhibit foetal transmission of the parasite was evaluated in a mouse model of congenital toxoplasmosis. Swiss mice were infected at mid-pregnancy with tachyzoites or cysts of the ME49 strain of T. gondii by intraperitoneal and oral route, respectively, and treated with SP230 at 50 mg/kg for 5 days by the same routes. Parasite burden in organs of dams and in foetuses was measured by quantitative PCR. Intraperitoneal administration of SP230 drastically reduced the number of parasites (more than 97% of reduction) in the brain and lungs of dams, and led to a reduction of 66% of parasite burden in foetuses. Oral administration of SP230 was particularly efficient with 97% of reduction of parasite burdens in foetuses. SP230 did not impact number and weight of offspring in our conditions. This inhibitor of TgCDPK1 is a promising candidate for the development of alternative therapeutics to treat infected pregnant women.

Toxoplasma gondii infection in domestic and wild felids as public health concerns: a systematic review and meta-analysis.

Felidae as definitive hosts for Toxoplasma gondii play a major role in transmission to all warm-blooded animals trough oocysts dissemination. Therefore the current comprehensive study was performed to determine the global status of T. gondii infection in domestic and wild felids aiming to provide comprehensive data of interest for further intervention approaching the One Health perspective. Different databases were searched by utilizing particular key words for publications related to T. gondii infecting domestic and wild feline host species, worldwide, from 1970 to 2020. The review of 337 reports showed that the seroprevalence of T. gondii in domestic cats and wild felids was estimated in 37.5% (95% CI 34.7-40.3) (I2 = 98.3%, P < 0.001) and 64% (95% CI 60-67.9) (I2 = 88%, P < 0.0001), respectively. The global pooled prevalence of oocysts in the fecal examined specimens from domestic cats was estimated in 2.6% (95% CI 1.9-3.3) (I2 = 96.1%, P < 0.0001), and that in fecal samples from wild felids was estimated in 2.4% (95% CI 1.1-4.2) (I2 = 86.4%, P < 0.0001). In addition, from 13,252 examined soil samples in 14 reviewed studies, the pooled occurrence of T. gondii oocysts was determined in 16.2% (95% CI 7.66-27.03%). The observed high rates of anti-T. gondii antibodies seroprevalence levels and oocyst excretion frequency in the felids, along with soil (environmental) contamination with oocysts may constitute a potential threat to animal and public health, and data will result of interest in further prophylaxis programs.

Epidemiologic and Public Health Significance of Toxoplasma gondii Infections in Venison: 2009-2020.

Toxoplasma gondii infections are common in humans and animals worldwide. The ingestion of food or water contaminated with oocysts excreted by infected cats or ingestion of uncooked or undercooked meat containing tissue cysts of T. gondii are the 2 major modes of transmission of T. gondii. Deer are a popular game. Recently, outbreaks of clinical toxoplasmosis were reported in humans in North America linked to ingestion of undercooked venison. Here, we review prevalence, persistence of infection, clinical disease, epidemiology, and public health risks of T. gondii infections in deer and other cervids for the past decade. Estimates of worldwide serological prevalence are summarized individually for each species of deer, elk, moose, and caribou. Genetic diversity of 112 viable isolates of T. gondii from cervids is discussed, including its public health significance. Prevalence of T. gondii in deer is very high. Any part of a deer, including liver, spleen, and muscles, should be cooked thoroughly before human consumption.

Toxoplasma gondii in mollusks and cold-blooded animals: a systematic review.

Toxoplasma gondii (T. gondii) is known for its ability to infect warm-blooded vertebrates. Although T. gondii does not appear to parasitize cold-blooded animals, the occurrence of T. gondii infection in marine mammals raises concerns that cold-blooded animals (frogs, toad, turtles, crocodiles, snakes, and fish) and shellfish are potential sources of T. gondii. Therefore, this systematic review aimed to determine the prevalence of T. gondii in mollusks and cold-blooded animals worldwide. We searched PubMed, ScienceDirect, ProQuest, Scopus, and Web of Science from inception to 1 August 2020 for eligible papers in the English language and identified 26 articles that reported the prevalence of T. gondii in mollusks and cold-blooded animals. These articles were subsequently reviewed and data extracted using a standard form. In total, 26 studies [involving 9 cross-sectional studies including 2988 samples of cold-blooded animals (129 positive cases for T. gondii) and 18 cross-sectional studies entailing 13 447 samples of shellfish (692 positive cases for T. gondii)] were included in this study. Although this study showed that shellfish and cold-blooded animals could be potential sources of T. gondii for humans and other hosts that feed on them, further investigations are recommended to determine the prevalence of T. gondii in shellfish and cold-blooded animals.

Clams and potential foodborne Toxoplasma gondii in Nunavut, Canada.

The prevalence of Toxoplasma gondii exposure in Inuit living in Nunavut (20%) is twice that of the US (11%); however, routes of exposure for Inuit communities in North America are unclear. Exposure to T. gondii in humans has been linked with consumption of raw or undercooked shellfish that can accumulate environmentally resistant oocysts. Bivalve shellfish, such as clams, are an important, nutritious, affordable and accessible source of food in many Northern Communities. To date, presence of T. gondii in clams in Northern Canada has not been reported. In this study, we tested for T. gondii presence in clams (Mya truncata) that were harvested in Iqaluit, Nunavut over a 1-week period in September 2016. Of 390 clams, eight (2.1%) were confirmed to contain T. gondii DNA (≥99.7% identity), as determined using polymerase chain reaction (PCR) and sequence confirmation. Additionally, three clams (0.8%) were confirmed to contain Neospora caninum-like DNA (≥99.2% identity). While N. caninum is not known to be a zoonotic pathogen, its presence in shellfish indicates contamination of the nearshore with canid faeces, and the potential for marine mammal exposure through marine food webs. Notably, the PCR assay employed in this study does not discriminate between viable and non-viable parasites. These findings suggest a possible route for parasite exposure through shellfish in Iqaluit, Nunavut. Future research employing viability testing will further inform public health messaging on the infectious potential of T. gondii in shellfish.

Foodborne transmission of Toxoplasma gondii infection in the last decade. An overview.

Toxoplasmosis is a zoonotic disease of global distribution and importance. It is caused by the protozoan parasite Toxoplasma gondii, the only species in the Toxoplasma genus. This parasite can infect most warm-blooded animals, including humans and livestock. Main routes of transmission are by ingestion of tissue cysts in raw or undercooked meat of infected animals, ingestion of raw vegetables or water contaminated with T. gondii oocysts from cat feces, and transplacental. Around one-third of human beings are chronically infected with T. gondii. Most infections appear to be asymptomatic in immunocompetent persons, but toxoplasmosis can be fatal to the fetus and immunocompromised adults. Water and foodborne outbreaks have been caused by this parasite worldwide, but few are well documented. Importantly, T. gondii is a parasite of high importance in animal health, causing reproductive failure, particularly in small ruminants, and clinical toxoplasmosis in many species. This overview discusses the knowledge of T. gondii infections in the last decade focusing on the foodborne transmission of this parasite.

Male-to-Female Presumed Transmission of Toxoplasmosis Between Sexual Partners.

Toxoplasmosis is one of the most widespread human parasitoses in developed countries. Sexual transmission has been confirmed in several animal species, and indirect evidence suggests it may occur in humans. We compared the seropositivity to Toxoplasma gondii in couples who visited the Center for Assisted Reproduction in Prague from June 2016 to June 2018 and analyzed various risk factors including the serological status of sexual partner. By comparing the risk factors in men and women, we tested the hypothesis of male-to-female sexual transmission of toxoplasmosis. The prevalence of toxoplasmosis in women with infected male partners (25.6%; n = 156) was higher than in women with uninfected male partners (18.2%; n = 477; P = 0.045). Therefore, a partner's seropositivity seems to be a risk factor for infection in women (n = 593; prevalence ratio = 1.418; P = 0.045) but not in men (n = 573; prevalence ratio = 1.058; P = 0.816). Our results support the hypothesis of the sexual transmission of T. gondii from men to women. The risk may seem relatively low, but transmission can occur during unprotected sexual intercourse, which may be at the time of conception. Because of the risk of congenital toxoplasmosis, a lower risk of infection than that observed in our study can represent a serious health problem.

Exposure to Toxoplasma gondii Through Consumption of Raw or Undercooked Meat: A Systematic Review and Meta-Analysis.

Toxoplasma gondii is a globally distributed protozoan that mainly causes health issues in the fetuses of pregnant women who have never been exposed to this parasite and patients with deficient immune systems. Except in these vulnerable populations, the primary infection generally goes unnoticed in most healthy individuals. Apart from transplant/transfusion, congenital transmission, direct contact with infected cats or their feces, and environmental contamination (i.e., oocysts in food, water, and soil) pathways, humans can acquire the parasite through consumption of animal tissues infected by T. gondii. This meta-analysis estimated the risk of acquiring T. gondii by consuming raw or undercooked meat, regardless of which animal species are eaten. Using a random-effect model, crude and adjusted pooled measures of association (risk and odds ratio) were estimated according to study design (cohort, case-control, and cross-sectional studies). The meta-analysis included measures of heterogeneity as well as quality rating scales for each study design. Our results suggest that individuals who eat raw or undercooked meat have, respectively, 1.2-1.3 times the risk and 1.7-3.0 times the odds of T. gondii infection compared to those who thoroughly cook meat, regardless of the animal species they consume. These results align with the current understanding that adequately cooking meat inactivates the parasite and decreases the risk of transmission. Seroprevalence ranged from 1.3% to 88.6%, while the proportion of individuals eating raw or undercooked meat fluctuated from 0.7% to 98.3% across the studies in the meta-analysis. These numbers reflect various preferences with regard to eating meat (i.e., eating tartar, sausages, or salamis) as well as individual, cultural and religious food habits, and personal awareness.

Toxoplasmosis: Recent Advances in Understanding the Link Between Infection and Host Behavior.

Humans, wildlife, and domestic animals are intimately linked through shared infections. Many parasites and pathogens use multiple host species, either opportunistically or sequentially, such that managing disease risk frequently requires a broader understanding of the ecological community. The coccidian protozoan Toxoplasma gondii infects more than one hundred species of vertebrates, ranging from bats to beluga whales. In humans, acute toxoplasmosis can have serious health consequences for immunocompromised individuals. Even amongst asymptomatic patients, however, toxoplasmosis has been linked to a range of behavioral alterations and conditions, such as changes in risk tolerance, neuroticism, mental illness, suicide, and accident proneness. Whether such links are causal or simply correlational has been the subject of intense study and debate; from an evolutionary standpoint, selection may favor parasite-induced alterations in host behavior that increase the likelihood a host is consumed by the definitive host-in this case a domestic or wild felid. Here, we examine current evidence for parasite-induced manipulations of host behavior, in both humans and other animals. We critically evaluate proposed mechanisms through which infection might influence host behavior, which range from inflammation in the brain to changes in hormones or neurotransmitters. Considering estimates that T. gondii may infect up to one-third of the global human population, we conclude by examining the implications of these changes for human behavior, individual fitness, and emergent cultural properties.

Transcriptional ups and downs: patterns of gene expression in the life cycle of Toxoplasma gondii.

Toxoplasma gondii reproduces sexually in felines and asexually in virtually all warm-blooded animals, including humans. This obligate intracellular parasite alternates between biologically distinct developmental stages throughout its complex life cycle. Stage conversion is crucial for T. gondii transmission, persistence, and the maintenance of genetic diversity within the species. Genome-wide comparative transcriptomic studies have contributed invaluable insights into the regulatory gene networks underlying T. gondii development.

Toxoplasma gondii seroprevalence in beef cattle raised in Italy: a multicenter study.

Toxoplasmosis represents an important public health issue, with the consumption of raw or undercooked meat being a major way of human infection. The role of beef in the transmission of the parasite to humans is questioned due to lower quantity of tissue cysts compared with other meat-producing species. However, the habit of consuming raw beef is regionally diffused, and the risk posed by Toxoplasma gondii infection in cattle should not be overlooked. Therefore, to update information on T. gondii in cattle reared in Italy, a multicentric seroepidemiological survey was designed and implemented in four Northern regions (Liguria, Lombardy, Piedmont, and Trentino Alto Adige) and Sardinia. Overall, a convenience sampling was performed, collecting 1444 serum samples from 57 beef cattle herds. Thirteen beef breeds were sampled, besides cross-breed; bovines age varied from 3 months to over 12 years. Sera were tested with a commercial ELISA for the detection of anti-T. gondii antibodies. Individual and herd data were analyzed by binary logistic regression analysis. A T. gondii seroprevalence of 10.2% was recorded, with differences among regions and values ranging from 5.3% in Liguria to 18.6% in the Piedmont region (p value = 0.0001). Both young and adult animals and males and females tested positive, without any significant difference (age and gender: p value > 0.05). Lower seroprevalence values were recorded in cattle born in Italy (8.7%) if compared with animals imported from abroad (13.4%) (p value = 0.046). The spread of T. gondii in beef cattle destined to Italian consumers is confirmed, suggesting the need of continuous monitoring of the infection.

Lights and Shadows of TORCH Infection Proteomics.

Congenital abnormalities cause serious fetal consequences. The term TORCH is used to designate the most common perinatal infections, where: (T) refers to toxoplasmosis, (O) means "others" and includes syphilis, varicella-zoster, parvovirus B19, zika virus (ZIKV), and malaria among others, (R) refers to rubella, (C) relates to cytomegalovirus infection, and (H) to herpes simplex virus infections. Among the main abnormalities identified in neonates exposed to congenital infections are central nervous system (CNS) damage, microcephaly, hearing loss, and ophthalmological impairment, all requiring regular follow-up to monitor its progression. Protein changes such as mutations, post-translational modifications, abundance, structure, and function may indicate a pathological condition before the onset of the first symptoms, allowing early diagnosis and understanding of a particular disease or infection. The term "proteomics" is defined as the science that studies the proteome, which consists of the total protein content of a cell, tissue or organism in a given space and time, including post-translational modifications (PTMs) and interactions between proteins. Currently, quantitative bottom-up proteomic strategies allow rapid and high throughput characterization of complex biological mixtures. Investigating proteome modulation during host-pathogen interaction helps in elucidating the mechanisms of infection and in predicting disease progression. This "molecular battle" between host and pathogen is a key to identify drug targets and diagnostic markers. Here, we conducted a survey on proteomic techniques applied to congenital diseases classified in the terminology "TORCH", including toxoplasmosis, ZIKV, malaria, syphilis, human immunodeficiency virus (HIV), herpes simplex virus (HSV) and human cytomegalovirus (HCVM). We have highlighted proteins and/or protein complexes actively involved in the infection. Most of the proteomic studies reported have been performed in cell line models, and the evaluation of tissues (brain, muscle, and placenta) and biofluids (plasma, serum and urine) in animal models is still underexplored. Moreover, there are a plethora of studies focusing on the pathogen or the host without considering the triad mother-fetus-pathogen as a dynamic and interconnected system.

Molecular Detection of Toxoplasma Gondii in Haemaphysalis Ticks in Korea.

Toxoplasma gondii are intracellular protozoa that can cause neurological disease or death in fetuses and even in immunocompromised human adults. Ticks are recognized as vectors of many microorganisms including viruses, bacteria, and protozoa. Recent studies detected T. gondii in various tick species in many countries. In this study, we performed PCR detection of the T. gondii B1 gene from Haemaphysalis ticks collected from vegetation in 4 localities, Wonju, Gunsan, Miryang, and Yangsan, in Korea. We analyzed DNA from 314 ticks (268 Haemaphysalis longicornis and 46 Haemaphysalis flava) and the B1 gene of T. gondii was detected in 13 of these. The detection of T. gondii in ticks differed significantly by region (P=0.021). T. gondii was detected in the following percentages of collected ticks: 3.7% (7 of 189) in Gunsan, 10% (5 of 50) in Wonju, 16.7% (1 of 6) in Yangsan, and 0% (0 of 69) in Miryang. The detection of T. gondii in ticks was not associated with tick species or development stage. This is the first report of T. gondii detection in ticks in Korea. Our results provide important information necessary to understand toxoplasmosis transmission.

Methods to assess the effect of meat processing on viability of Toxoplasma gondii: towards replacement of mouse bioassay by in vitro testing.

Consumption of meat containing viable tissue cysts is considered one of the main sources of human infection with Toxoplasma gondii. In contrast to fresh meat, raw meat products usually undergo processing, including salting and mixing with other additives such as sodium acetate and sodium lactate, which affects the viability of T. gondii. However, the experiments described in the literature are not always performed in line with the current processing methods applied in industry. It was our goal to study the effect of salting and additives according to the recipes used by industrial producers. Mouse or cat bioassay is the 'gold standard' to demonstrate the presence of viable T. gondii. However, it is costly, time consuming and for ethical reasons not preferred for large-scale studies.Therefore, we first aimed to develop an alternative for mouse bioassay that can be used to determine the effect of processing on the viability of T. gondii tissue cysts. The assays studied were (i) a cell culture method to determine the parasite's ability to multiply, and (ii) a propidium monoazide (PMA) dye-based assay to selectively detect DNA from intact parasites. Processing experiments were performed with minced meat incubated for 20 h with low concentrations of NaCl, sodium lactate and sodium acetate. NaCl appeared to be the most effective ingredient with only one or two out of eight mice infected after inoculation with pepsin-digest of portions processed with 1.0, 1.2 and 1.6% NaCl. Results of preliminary experiments with the PMA-based method were inconsistent and did not sufficiently discriminate between live and dead parasites. In contrast, the cell culture method showed promising results, but further optimization is needed before it can replace or reduce the number of mouse bioassays needed. In future, standardised in vitro methods are necessary to allow more extensive testing of product-specific processing methods, thereby providing a better indication of the risk of T. gondii infection for consumers.

Toxoplasma-induced Behavioral Changes: An Aspecific Consequence of Neuroinflammation.

A key strategy that many parasites use to facilitate transmission involves behavioral modification of their hosts. Toxoplasma gondii has been taken as an example for this strategy. A recent study by Boillat et al. reported that attraction to predator odor following Toxoplasma infection is not specific to felines.

Comparison of consumer knowledge about Campylobacter, Salmonella and Toxoplasma and their transmissibility via meat: results of a consumer study in Germany.

BACKGROUND: Campylobacter is the most commonly reported causative agent of foodborne bacterial infection in Germany, and contaminated chicken meat is an important source of this zoonotic agent. The aim of this study was to determine the knowledge of consumers in Germany about Campylobacter, Salmonella and Toxoplasma and their transmissibility via meat. In addition, we investigated the level of knowledge between selected consumer groups and whether the results coincided with those of international studies. METHODS: We conducted a cross-sectional survey of 1008 consumers in Germany via an online panel to record, analyse and evaluate the state of knowledge about Campylobacter, Salmonella and Toxoplasma. The participants were selected according to age, gender and federal states to be representative of the German population. RESULTS: Overall, 68.3% of the respondents had never heard of Campylobacter, 20.2% had heard of Campylobacter but did not know how to protect themselves, and only 11.5% knew how to protect themselves from Campylobacter infections. Slightly more than half (52.2%) of the respondents who had at least heard of Campylobacter knew that Campylobacter was transmissible via meat. Knowledge increased significantly with age. Participants over 60 years old knew about Campylobacter almost three times as often as the 16- to 19-year-old comparison group (OR = 2.982). Consumers who had at least a secondary school certificate were almost twice as likely to know about Campylobacter as those who had no school certificate or a lower secondary school certificate (OR = 1.899). Participants who were not actors in the food chain were significantly less frequently informed about Campylobacter than were those who were actors in the food chain. Consumer knowledge of Toxoplasma was better than that of Campylobacter. Consumers have the most knowledge about Salmonella. CONCLUSIONS: Consumers in Germany are predominantly poorly informed about Campylobacter and the transmission route via meat. General knowledge of Toxoplasma is better than that of Campylobacter. Among the three pathogens, consumers are best informed about Salmonella. This finding highlights the importance of making existing information materials more accessible to consumers in the future to increase their knowledge, with the objective of reducing the incidence of Campylobacter infections.

Neuroinflammation-Associated Aspecific Manipulation of Mouse Predator Fear by Toxoplasma gondii.

In rodents, the decrease of felid aversion induced by Toxoplasma gondii, a phenomenon termed fatal attraction, is interpreted as an adaptive manipulation by the neurotropic protozoan parasite. With the aim of understanding how the parasite induces such specific behavioral modifications, we performed a multiparametric analysis of T. gondii-induced changes on host behavior, physiology, and brain transcriptome as well as parasite cyst load and distribution. Using a set of complementary behavioral tests, we provide strong evidence that T. gondii lowers general anxiety in infected mice, increases explorative behaviors, and surprisingly alters predator aversion without selectivity toward felids. Furthermore, we show a positive correlation between the severity of the behavioral alterations and the cyst load, which indirectly reflects the level of inflammation during brain colonization. Taken together, these findings refute the myth of a selective loss of cat fear in T. gondii-infected mice and point toward widespread immune-related alterations of behaviors.