Toxoplasma Infection Research Articles

Seroprevalence of ocular toxoplasmosis in a major referral eye center in Southwest, Nigeria

Objective: To assess the prevalence of ocular toxoplasmosis by seroprevalence of Toxoplasma (T.) gondii among people attending the referral eye center in Southwest Nigeria, and to identify associated risk factors and socio-economic determinants related to ocular toxoplasmosis. Methods: A systematic questionnaire was used and blood samples of 3 mL each were taken. Serological tests of anti-T. gondii IgG and IgM antibodies were performed using the ELISA kit. Eye examinations were performed. Results: T. gondii antibodies were detected in 52.6% of the tested patients. A total of 409 respondents were surveyed. The prevalence of toxoplasmosis increased with age which was statistically significant (P=0.001). The highest prevalence was found in farmers (69.2%, P=0.011). The overall prevalence of ocular toxoplasmosis within the study area was 1.7%. Conclusions: The high seroprevalence recorded in this study is suggestive of the endemic nature of the disease. Awareness among the populace about Toxoplasma infection is imperative in understanding the epidemiology of the infection.

Analysis of the Correlation Between Toxoplasma gondii Seropositivity and Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial brain disorder and infectious diseases are considered as one of the predisposing factors for AD. Toxoplasma gondii, an obligate intracellular parasitic protozoan, is suspected of being associated with AD. Serum samples were collected from 109 AD patients and 114 age-matched healthy controls. ELISA was performed using recombinant T. gondii cyst wall protein 1 (CST1) to detect T. gondii antibodies. A parallel experiment was performed with Toxoplasma gondii tachyzoites lysate protein. To analyze whether factors associated with the onset of AD included chronic T. gondii infection, a multivariate logistic regression model was applied, further validating the correlation between chronic T. gondii infection and AD. AD patients exhibited significantly higher levels of Toxoplasma-specific antibodies in their serum compared to the control group, with statistically significant differences (p < 0.05). Multivariate logistic regression analysis revealed that Toxoplasma infection is a risk factor for AD (p < 0.01), and the CST1 antigen can significantly improve the model's performance in predicting the occurrence of AD. The results indicate that chronic infection with Toxoplasma gondii could be one of the risk factors for the development of AD, potentially predisposing individuals with underlying health conditions to the disease. This further validates the correlation between Toxoplasma gondii and AD.

Associations of exposure to blood heavy metal mixtures with Toxoplasma infection among U.S. adults: a cross-sectional study.

Research increasingly links environmental exposure to toxic metals with health risks, yet the effect of combined metal exposure on Toxoplasma infection remains underexplored. This study investigates the relationship between concurrent heavy metal exposure and Toxoplasma infection in adults. We analyzed data from 10,746 adults aged 20-80 from NHANES, with 1,869 positive for Toxoplasma gondii IgG. The study assessed associations between lead (Pb), cadmium (Cd), and mercury (Hg) with Toxoplasma infection risk using single-metal logistic regression, RCS analysis, WQS regression, and qgcomp models. Each metal showed an independent association with Toxoplasma infection risk. Pb had a non-linear association, while Hg had a linear one. Analysis of multiple metals indicated a positive correlation between heavy metal exposure and infection risk, particularly in younger and middle-aged adults, with Pb showing the strongest link. Our findings reveal a significant association between heavy metal exposure and Toxoplasma infection risk, especially in younger demographics, with lead being a key factor. This highlights the importance of understanding environmental metal exposure's impact on public health and informs the development of prevention strategies.

Mitigating cognitive impairment in people with HIV by targeting potential impacts of toxoplasmic infection

Mitigating cognitive impairment in people with HIV by targeting potential impacts of toxoplasmic infection

Dynamics of amylopectin granule accumulation during the course of the chronic Toxoplasma infection is linked to intra-cyst bradyzoite replication.

The contribution of amylopectin granules (AG), comprised of a branched chain storage homopolymer of glucose, to the maintenance and progression of the chronic Toxoplasma gondii infection has remained undefined. Here we describe the role of AG in the physiology of encysted bradyzoites by using a custom developed imaging-based application AmyloQuant that permitted quantification of relative levels of AG within in vivo derived tissue cysts during the initiation and maturation of the chronic infection. Our findings establish that AG are dynamic entities, exhibiting considerable heterogeneity among tissue cysts at all post infection time points examined. Quantification of relative AG levels within tissue cysts exposes a previously unrecognized temporal cycle defined by distinct phases of AG accumulation and utilization over the first 6 weeks of the chronic phase. This AG cycle is temporally coordinated with overall bradyzoite mitochondrial activity implicating amylopectin in the maintenance and progression of the chronic infection. In addition, the staging of AG accumulation and its rapid utilization within encysted bradyzoites was associated with a burst of coordinated replication. As such our findings suggest that AG levels within individual bradyzoites, and across bradyzoites within tissue cysts may represent a key component in the licensing of bradyzoite replication, intimately linking stored metabolic potential to the course of the chronic infection. This extends the impact of AG beyond the previously assigned role that focused exclusively on parasite transmission. These findings force a fundamental reassessment of the chronic Toxoplasma infection, highlighting the critical need to address the temporal progression of this crucial stage in the parasite life cycle.

Diffusion Tensor Imaging of the Auditory Pathway in Prelingual Deaf Children in Comparison to Normal Hearing Children in the 1 to 7 Years of Age Group

Abstract Objective This article aims to determine the microstructural alterations in the auditory pathway in prelingual deaf children using diffusion tensor imaging (DTI)-derived parameters—fractional anisotropy (FA) and apparent diffusion coefficient (ADC), and secondarily to evaluate these changes in rubella and cytomegalovirus (CMV) positive cases. Method A consecutive series of consenting deaf and normal children between 1 and 7 years of age, forming the case and control groups, respectively, underwent DTI, audiological tests, and testing for rubella, CMV, and toxoplasma infections. FA and ADC were measured at four locations bilaterally: lateral lemniscus (LL), inferior colliculus, medial geniculate body, and auditory cortex (AC). Result The mean ADC values were higher and the mean FA values were lower in cases (19 males, 21 females, mean age 2.65 years) than the controls (21 males, 19 females, mean age 4.63 years) at all eight sites. Sixteen (40%), 17 (42.5%), and 7 (17.5%) cases had severe, severe to profound, and profound hearing loss, respectively, the FA and ADC values being significantly different for LL. For rubella and CMV immunoglobulin G, 20/40and 17/40 cases were positive, respectively, 11 for both, and none for toxoplasma. Significant decrease in FA was seen at LL and AC in rubella/CMV positive cases. Conclusion Microstructural changes are seen throughout the auditory pathway in prelingual deaf children, especially with rubella and/or CMV positive status. Further studies may pave the path to segregate out patient groups potentially more responsive to cochlear implant.

Toxoplasma WH3 Δrop18 acts as a live attenuated vaccine against acute and chronic toxoplasmosis

Toxoplasma gondii is a significant zoonotic pathogen of toxoplasmosis in humans and animals. Here a live attenuated Toxoplasma vaccine of WH3 Δrop18 was developed. The results showed that all mice vaccinated with WH3 Δrop18 were able to survive when challenge with various strains of Toxoplasma, including RH (type I), ME49 (type II), WH3 or WH6 (type Chinese 1). No cysts, if few, in the brain of the vaccinated animals were seen after challenge with cyst forming strains of ME49 or WH6. Vaccination with the WH3 Δrop18 triggered a strong immune response, including significantly increased level of the cytokines (IFN-γ, IL-12, TNF-α and IL-10) and the activation of CD4+ and CD8+ T-lymphocytes and long term of specific antibodies against Toxoplasma. Our results strongly indicate that vaccine of WH3 Δrop18 might provide effective immune protection against a wide range strains of Toxoplasma infections and be a promising live attenuated vaccine candidate.

T lymphocyte-dependent IL-10 down-regulates a cytokine storm driven by Toxoplasma gondii GRA24.

As a model organism in the study of immunity to infection, Toxoplasma gondii has been instrumental in establishing key principles of host anti-microbial defense and its regulation. Here, we employed an attenuated uracil auxotroph strain of Type I Toxoplasma designated OMP to further untangle the early immune response to this parasitic pathogen. Experiments using αβ T cell-deficient Tcrb-/- mice unexpectedly revealed that an intact αβ T lymphocyte compartment was essential to survive infection with OMP. Subsequent antibody depletion and knockout mouse experiments demonstrated contributions from CD4+ T cells and most predominantly CD8+ T cells in resistance. Using transgenic knockout mice, we found only a partial requirement for IFN-γ and a lack of requirement for Toll-like receptor (TLR) adaptor MyD88 in resistance. In contrast to other studies on Toxoplasma, the ability to survive OMP infection did not require IL-12p40. Surprisingly, T cell-dependent IL-10 was found to be critical for survival, and deficiency of this cytokine triggered an abnormally high systemic inflammatory response. We also found that parasite molecule GRA24, a dense granule protein that triggers TLR-independent IL-12 production, acts as a virulence factor contributing to death of OMP-infected Tcrb-/- and IL-10-/- mice. Furthermore, resistance against OMP was restored in Tcrb-/- mice via monoclonal depletion of IL-12p40, suggesting that GRA24-induced IL-12 underlies the fatal immunopathology observed. Collectively, our studies provide insight into a novel and rapidly arising T lymphocyte-dependent anti-inflammatory response to T. gondii which operates independently of MyD88 and IL-12 and that depends on the function of parasite-dense granule protein GRA24.IMPORTANCEAs a model infectious microbe and an important human pathogen, the apicomplexan Toxoplasma gondii has provided many important insights into innate and adaptive immunity to infection. We show here that a low virulence uracil auxotrophic Toxoplasma strain emerges as a virulent parasite in the absence of an intact T cell compartment. Both CD4+ and CD8+ T lymphocytes are required for optimal protection, in line with previous findings in other models of Toxoplasma infection. Nevertheless, several novel aspects of the response were identified in our study. Protection occurs independently of IL-12 and MyD88 and only partially requires IFN-γ. This is noteworthy particularly because the cytokines IL-12 and IFN-γ have previously been regarded as essential for protective immunity to T. gondii. Instead, we identified the anti-inflammatory effects of T cell-dependent IL-10 as the critical factor enabling host survival. The parasite dense granule protein GRA24, a host-directed mitogen-activated protein kinase activator, was identified as a major virulence factor in T cell-deficient hosts. Collectively, our results provide new and unexpected insights into host resistance to Toxoplasma.

Disseminated Toxoplasma Gondii Infection in a Deceased Donor Kidney Transplant Recipient: A Fatal Case Report

Abstract Introduction/Objective Post-transplant immunosuppression predisposes patients to severe complications from opportunistic infections, including Toxoplasma gondii. Typically asymptomatic and self-limited in immunocompetent individuals, Toxoplasma gondii can cause life-threatening disseminated disease in immunocompromised patients like solid organ transplant recipients. The challenge in diagnosing Toxoplasmosis is further exacerbated in patients receiving prophylactic therapy with agents such as Atovaquone, which may mask clinical suspicion. This case report describes a fatal presentation of disseminated Toxoplasmosis in a kidney transplant recipient. Methods/Case Report A 44-year-old male with a history of deceased donor kidney transplant presented to the emergency department two months post-transplant with symptoms of malaise, shortness of breath, hypoxemia, and hypotension. Despite medical interventions, the patient deteriorated rapidly, developing acute hypoxemic respiratory failure and septic shock requiring intubation. Subsequently, he succumbed to multisystem organ failure five days after admission. The autopsy revealed disseminated Toxoplasma gondii infection, with tachyzoites/bradyzoites identified in multiple organs, including the brain, bone marrow, and lymph nodes. Positive Toxoplasma immunohistochemical staining and PCR confirmed the diagnosis. Results (if a Case Study enter NA) NA Conclusion Toxoplasma infection in post-transplant patients can manifest as a severe and potentially fatal complication. Dissemination can arise from the reactivation of latent infection, donor transmission, or new acquisition. In this case, the infection likely resulted from the reactivation of latent infection in the donor, compounded by immunosuppression in the recipient. Notably, the patient received Atovaquone prophylaxis due to a sulfa allergy. Nonetheless, the case highlights the potential for delayed diagnosis due to atypical presentations in immunocompromised patients. Clinicians should maintain a high index of suspicion for Toxoplasma infection in post- transplant patients, particularly in those with unexplained clinical deterioration. This case emphasizes the importance of maintaining a high index of suspicion for T. gondii infection in post-transplant patients, even in those receiving prophylaxis.

The Utility of Serologic TORCH Testing During Pregnancy for Maternal-related Versus Fetal-related Indications: A Retrospective Study.

Clear guidelines have not been established about the utility of TORCH serology testing in women for whom TORCH infection is suspected according to clinical and laboratory manifestations during pregnancy. We aimed to compare rates of TORCH infections [specifically cytomegalovirus (CMV), Toxoplasma and rubella] in women who underwent TORCH serology testing due to maternal- versus fetal-related indications. This 10-year single-center retrospective study included all the women beyond 24 weeks of gestation who underwent TORCH serology testing due to maternal- or fetal-related indications. Maternal-related indications included fever, gastroenteritis, elevated liver enzymes and thrombocytopenia. Fetal-related indications included intrauterine growth restriction, polyhydramnios and oligohydramnios. During the study period, 304 women underwent TORCH serology testing due to maternal-related indications and 771 due to fetal-related indications. For the maternal-related compared with the fetal-related indication group, maternal and congenital TORCH infections were more prevalent (P = 0.015), specifically CMV (P = 0.036). Eight (2.6%) of the women with maternal-related indications had a primary TORCH infection; 4 of them (50%) had concomitant congenital infections. Six (0.8%) of the women with fetal-related indications had a primary infection; none had a related congenital infection. Among the women with maternal-related indications, higher rates of maternal TORCH infection were found among those with thrombocytopenia (7.1%) and elevated liver enzymes (3.0%). During the study period, maternal-indicated TORCH testing detected 10.8% of neonates born with a confirmed TORCH infection. The clinical yield of TORCH serology for nonspecific sonographic fetal features was low. Nonetheless, maternal-related indications should prompt testing for CMV and Toxoplasma infection.

Toxoplasma qPCR kinetics to guide pre-emptive treatment of toxoplasmosis after allogeneic hematopoietic stem cell transplantation.

Recent ECIL-guidelines recommend a quantitative PCR (qPCR) guided pre-emptive treatment approach to toxoplasmosis in seropositive recipients of allogeneic hematopoietic cell transplantation (allo-HCT). While qPCR might serve as a sensitive tool for early Toxoplasma detection, its role in treatment follow-up remains unknown. We analyzed the qPCR kinetics of allo-HCT recipients experiencing either Toxoplasma infection (TI, n=71) or disease (TD, n=14) in relation to different parameters. We included 85 patients with available qPCR values expressed as quantitative cycle (Cq) from four large hematological centers from 2009 to 2023, and kinetic analysis was performed in a selection of 74 patients screened at least weekly with blood qPCR. Day 0 (D0) was the day of anti-Toxoplasma treatment start or (when untreated) day of diagnosis. Time to qPCR negativity was inversely proportional to the Cq value at D0 (p=0.0063). Not reaching negativity at D10 was associated with a significantly higher mortality at D30 (p=0.023). Patients with a high D0-parasitic load and patients with TD showed slower clearance (p<0.001, p=0.032). Time to negativity was not significantly different for patients started on prophylactic vs curative doses as first-line treatment regimen (p=0.16). This study underscores the predictive value of qPCR kinetics monitoring in allo-HCT patients with toxoplasmosis. With the aforementioned risk factors, clinicians can identify patients at high-risk for worse outcome. Our results support to consider a therapeutic change or reinforcement if the parasitic load does not decrease after 10 days, supplementing existing clinical guidelines.

Impact of Toxoplasma gondii on Serum Protein Levels and Mineral Content in Sheep and Goats at a Small Dairy Farm in White Nile State, Sudan

Aim: This study aims to investigate the effects of Toxoplasma gondii infection on the serum proteins and macro elements (Sodium, Potassium, Calcium, Magnesium and Phosphate) for sheep and goat. Introduction: In sheep and goats, Toxoplasma infection is a major cause of abortion and stillbirth. Subclinical infections are also quite common in adult animals of affected flocks and herds. Serum proteins and macro elements plays an essential role in animal metabolism. Materials and Methods: Serological survey of T. gondii was conducted using Latex Agglutination Test (LAT) for 20 sera collected from sheep and goats (8 and12 respectively) in white Nile State, Sudan. Results: Out of twelve goats’ serum and eight sheep serum samples, seven samples were found to be positive for Toxoplasma (58.33%) in goats and four samples were found to be positive for Toxoplasma (50%) in sheep, the remaining samples were negative. It was observed that serum Total protein (Tp) level was increased significantly (p&lt;0.05) in both species, and albumin (Alb) level decreased significantly (p&lt;0.05) in goats, while Globulin (Glob) was significantly (p&lt;0.05) low in sheep compared with control animals. The results showed that some minerals (Na and K) concentrations in the serum were higher in both sheep and goats compared to the controls. Conclusion: In conclusion infestation of goats with Toxoplama gondii increases the total protein, globulins and significantly decreases the albumin concentrations. For sheep the infestation increases the total protein, albumin and significantly decreases the globulin concentrations. Sheep and goats infected with Toxoplasma gondii showed increased serum sodium, potassium and magnesium levels affecting most of the enzyme systems.

Associations between Fetal Symptoms during Pregnancy and Neonatal Clinical Complications with Toxoplasmosis.

Toxoplasmosis is a parasitism transmitted by Toxoplasma gondii, part of the TORCH complex, the most prevalent parasitism worldwide. It is asymptomatic in immunocompetent individuals but causes severe infections and developmental abnormalities in pregnant women, mainly affecting the central nervous system and the gastrointestinal system. In our prospective study, we analyzed cases of recent maternal Toxoplasma infections confirmed by serological testing between 1996 and 2020 at the Department of Obstetrics and Gynecology, Semmelweis University. Amniocentesis, followed by PCR, was performed in cases of recent infection confirmed by serological testing during pregnancy. After birth, a neonatological, microbiological, pediatric neurological and ophthalmological examination and a follow-up was carried out. During the study period, a total of 238 cases of amniotic fluid Toxoplasma PCR testing due to Toxoplasma recent infection were performed. In terms of pregnancies, there were 219 deliveries and seven abortions. Twelve cases had no data available on the outcome of the pregnancy. In total, 133 cases of ultrasound abnormalities were detected during pregnancy, while in 105 cases, no abnormalities were detected on ultrasound examination. During amniocentesis, eight cases of Toxoplasma infection were revealed in amniotic fluid samples by PCR, and in 230 cases, the result was negative. Neonatal follow-up was performed in 139 cases, with no abnormalities during follow-up in 117 cases, and in 22 cases, there was a detectable complication that was likely to be related to Toxoplasma infection. In all 22 cases, amniotic fluid PCR Toxoplasma testing was negative. The most common ultrasound abnormalities involve the nervous system and the gastrointestinal system. In cases of suspicion, it is recommended to perform amniocentesis Toxoplasma PCR testing besides the indirect methods to help the pregnant woman decide whether to carry the pregnancy to term. During follow-up, a multidisciplinary team experienced in pregnancies complicated by toxoplasmosis must carry out the follow-up, care and subsequent development.

EP142 - "Unravelling the Enigma: Navigating the Diagnostic Dilemma of Abdominal Toxoplasmosis"

Abstract Introduction Abdominal toxoplasmosis, an infrequent yet medically significant manifestation of Toxoplasma infection, primarily caused by the protozoan parasite Toxoplasma gondii. Although toxoplasmosis can affect various organs, its occurrence in the abdominal region introduces unique diagnostic complexities, presenting symptoms such as abdominal pain, gastrointestinal disruptions, and systemic complications. Case Report In a notable case, a middle-aged patient presented with perplexing gastrointestinal symptoms, including nausea, vomiting, abdominal pain, and irregular bowel habits. With a history of anaemia and thrombocytopenia necessitating transfusions and yielding inconclusive bone marrow biopsies, the patient underwent OGD and colonoscopy with biopsies during initial management, revealing a hiatus hernia and diverticulosis that did not explain the symptoms. Despite being discharged pending biopsy results, subsequent normal findings failed to clarify. Upon readmission with persistent gastrointestinal complaints, a CTAP revealed two suspicious neoplastic focal areas of small bowel wall thickening and enlarged mesenteric lymph nodes. The MDT discussions ensued to rule out malignancy, leading to a follow-up PET scan suggesting nodal disease, raising concerns about lymphoma, small bowel adenocarcinoma, or carcinoid tumour and recommended an ultrasound-guided lymph node biopsy, 5 HIAA if asymptomatic, and diagnostic laparoscopy if symptomatic or obstructed. Subsequent core biopsy of a neck lymph node unveiled appearances consistent with toxoplasmosis, prompting treatment with anti-parasitic drugs. The patient awaits capsule endoscopy, and a follow-up CT scan displayed a reduction in bowel lesions and lymph nodes. Conclusion This case highlights the swift and precise identification of toxoplasmosis, resulting in an optimal patient outcome. The clinical manifestations of toxoplasmosis are diverse and lack distinct characteristics, making it challenging to definitively diagnose, particularly in immunocompetent individuals.

Association of toxoplasma infection and susceptibility with NLRP1 rs8081261 and rs11652907 gene polymorphism using RFLP among Egyptian population.

Association of toxoplasma infection and susceptibility with NLRP1 rs8081261 and rs11652907 gene polymorphism using RFLP among Egyptian population.

Enzymatically enhanced ultrastructure expansion microscopy unlocks expansion of in vitro Toxoplasma gondii cysts.

Toxoplasma gondii is an intracellular parasite capable of establishing long-term chronic infection in nearly all warm-blooded animals. During the chronic stage, parasites encapsulate to form cysts predominantly in neurons and skeletal muscle. Current anti-Toxoplasma drugs do not eradicate chronic parasites, leaving a reservoir of infection. The cyst is critical for disease transmission and pathology, yet it is harder to study, with the function of many chronic-stage proteins still unknown. Ultrastructure expansion microscopy, a new method to overcome the light microscopy's diffraction limit by physically expanding the sample, allowed in-depth studies of acute Toxoplasma infection. We show that Toxoplasma cysts resist expansion using standard protocol, but an additional enzymatic digestion with the mucinase StcE allows full expansion. This protocol offers new avenues for examining the chronic stage, including precise spatial organization of cyst-specific proteins, linking these locations to morphological structures, and detailed investigations of components of the durable cyst wall.

Seeing the unseen: illuminating Toxoplasma gondii's metabolic manipulation.

Intracellular infection by a pathogen induces significant rewiring of host cell signaling and biological processes. Understanding how an intracellular pathogen such as Toxoplasma gondii modulates host cell metabolism with single-cell resolution has been challenged by the variability of infection within cultures and difficulties in separating host and parasite metabolic processes. A new study from Gallego-Lopez and colleagues (G. M. Gallego-López, E. C. Guzman, D. E. Desa, L. J. Knoll, M. C. Skala, mBio e00727-24, 2024, https://doi.org/10.1128/mbio.00727-24) applies a quantitative imaging approach to evaluate the host cell metabolism during intracellular infection with Toxoplasma. This study provides important insights into host metabolic responses to Toxoplasma infection and offers a valuable tool to dissect the mechanisms underlying parasite infection and pathophysiology.

Longitudinal Study of Cognitive Function in People with HIV and Toxoplasmic Encephalitis or Latent toxoplasma Infection.

Neurocognitive impairment (NCI) may occur during and persist even after recovery from HIV-related CNS co-infections such as toxoplasmic encephalitis (TE). The long-term cognitive effects of TE and latent toxoplomasmic infections (LTI) among persons with HIV (PWH) are unknown. We measured longitudinal effects on NC functioning in PWH with TE compared to LTI or no toxoplasmal infection. PWH (n = 345) followed in two longitudinal cohort studies underwent comprehensive neurocognitive assessments and an anti-Toxoplamic IgG assay. Participants were classified into one of three groups: TE+ (n = 39), LTI+ (n = 34), LTI- (n = 272). The primary outcome was change in neurocognitive function between baseline and 7-year visit. The mean age was 48 ± 11 years, mean educational level 13 ± 3 years, and 13% were female. TE+ patients were less likely to have undetectable viral loads (≤50 copies/mL) and had lower absolute CD4 counts. The TE+ group had the highest prevalence of NCI globally and in domains of verbal, executive function, learning, recall, working memory, processing speed and motor at baseline and at 7-year follow-up. Changes in longitudinal NC function over 7 years were small and did not differ significantly among all groups, except that speed of information processing improved more in TE+ compared with LTI- participants. PWH with a history of TE had cognitive impairment over a broad range of severity at both baseline and last follow-up. Changes in cognition from baseline to last examination in all groups were minimal and did not differ significantly among the groups with the exception of speed of information processing.

Toxoplasma infection induces an aged neutrophil population in the CNS that is associated with neuronal protection

BackgroundInfection with the protozoan parasite Toxoplasma gondii leads to the formation of lifelong cysts in neurons that can have devastating consequences in the immunocompromised. In the immunocompetent individual, anti-parasitic effector mechanisms and a balanced immune response characterized by pro- and anti-inflammatory cytokine production establishes an asymptomatic infection that rarely leads to neurological symptoms. Several mechanisms are known to play a role in this successful immune response in the brain including T cell production of IFNγ and IL-10 and the involvement of CNS resident cells. This limitation of clinical neuropathology during chronic infection suggests a balance between immune response and neuroprotective mechanisms that collectively prevent clinical manifestations of disease. However, how these two vital mechanisms of protection interact during chronic Toxoplasma infection remains poorly understood.Main textThis study demonstrates a previously undescribed connection between innate neutrophils found chronically in the brain, termed “chronic brain neutrophils” (CBNeuts), and neuroprotective mechanisms during Toxoplasma infection. Lack of CBNeuts during chronic infection, accomplished via systemic neutrophil depletion, led to enhanced infection and deleterious effects on neuronal regeneration and repair mechanisms in the brain. Phenotypic and transcriptomic analysis of CBNeuts identified them as distinct from peripheral neutrophils and revealed two main subsets of CBNeuts that display heterogeneity towards both classical effector and neuroprotective functions in an age-dependent manner. Further phenotypic profiling defined expression of the neuroprotective molecules NRG-1 andErbB4 by these cells, and the importance of this signaling pathway during chronic infection was demonstrated via NRG-1 treatment studies.ConclusionsIn conclusion, this work identifies CBNeuts as a heterogenous population geared towards both classical immune responses and neuroprotection during chronic Toxoplasma infection and provides the foundation for future mechanistic studies of these cells.

Impact of toxoplasma infection on vitamin D level in Iraqi women- A cross sectional study

Impact of toxoplasma infection on vitamin D level in Iraqi women- A cross sectional study