Immunocompetent Individuals Research Articles

Potential relationship between cytomegalovirus and immunosenescence: Evidence from observational studies.

Immunosenescence (IS) occurs as a natural outcome of ageing and may be described as a decline in immune system flexibility and adaptability to sufficiently respond to new, foreign antigens. Potential factors that may precipitate IS include persistent herpesvirus infections, such as cytomegalovirus (CMV). Here, we conducted a review of the literature evaluating the potential association between CMV and IS. Twenty-seven epidemiologic studies that included direct comparisons between CMV-seropositive and CMV-seronegative immunocompetent individuals were analysed. The majority of these studies (n=20) were conducted in European populations. The strength of evidence supporting a relationship between CMV, and various IS-associated immunologic endpoints was assessed. T-cell population restructuring was the most prominently studied endpoint, described in 21 studies, most of which reported a relationship between CMV and reduced CD4:CD8 T-cell ratio or modified CD8+ T-cell levels. Telomere length (n=4) and inflammageing (n=3) were less frequently described in the primary literature, and the association of these endpoints with CMV and IS was less pronounced. An emergent trend from our review is the potential effect modification of the CMV-IS relationship with both sex and age, indicating the importance of considering various effector variables when evaluating associations between CMV and IS. Our analysis revealed plausible mechanisms that may underlie the larger epidemiologic trends seen in the literature that support the indirect effect of CMV on IS. Future studies are needed to clarify CMV-associated and IS-associated immunologic endpoints, as well as in more diverse global and immunocompromised populations.

PRIMARY CUTANEOUS ASPERGILLOSIS IN A 13-YEAR-OLD BOY WITH BONE MARROW APLASIA: CASE REPORT

Cutaneous aspergillosisis a rare condition, and while rare in immunocompetent individuals, it predominantly affects immunosuppressed patients, particularly those with hematological-oncological disorders within the pediatric demographic. Herein, we present a 13-year-old boy under follow-up for bone marrow aplasia. The child developed long-lasting fever and papulous and ulcerous indurated skin lesions on his whole body. Blood count showed agranulocytosis with neutrophils count of 10/μl. Thoracic, abdominal and pelvic Computed Tomography (CT) scan has revealed bilateral alveolar syndrome in the lungs. Skin biopsy revealed cutaneous aspergillosis. Despite treatment, the boys condition did not improve, and he passed away 2 weeks following his hospital admission because of septic shock. Cutaneous aspergillosis is due to Aspergillus flavus and A. fumigatus, for primary and secondary (invasive) cases, respectively. The rapid progression of this disease from the initial cutaneous infectious region necessitates prompt medical intervention to avoid increasing the risk of mortality. This condition typically manifests after the fungus is directly inoculated through skin contact with contiguous infected areas or via hematogenous spread from a remote mycotic site to the skin.

Adjuvant ArtinM favored the host immunity against Cryptococcus gattii infection in C57BL/6 mice.

Aim: Cryptococcus gattii causes a severe fungal infection with high mortality rate among immunosuppressed and immunocompetent individuals. Due to limitation of current antifungal treatment, new immunotherapeutic approaches are explored.Methods: This study investigated an immunization strategy utilizing heat-inactivated C. gattii with ArtinM as an adjuvant. C57BL/6 mice were intranasally immunized with heat-killed C. gattii and ArtinM was administrated either before immunization or along with HK-C. gattii. Mice were infected with C. gattii and the efficacy of the immunization protocol was evaluated.Results: Mice that received ArtinM exhibited increased levels of IL-10 and relative expression of IL-23 in the lungs, reduced fungal burden and preserved tissue integrity post-infection.Conclusion: Adjuvant ArtinM improved immunization against C. gattii infection in C57BL/6 mice.

LasR regulates protease IV expression at suboptimal growth temperatures in Pseudomonas aeruginosa.

The opportunistic pathogen Pseudomonas aeruginosa causes debilitating lung infections in people with cystic fibrosis, as well as eye, burn, and wound infections in otherwise immunocompetent individuals. Many of P. aeruginosa's virulence factors are regulated by environmental changes associated with human infection, such as a change in temperature from ambient to human body temperature. One such virulence factor is protease IV (PIV). Interestingly, piv expression is higher at ambient temperatures (22-28°C) compared to human body temperature (37°C). We found that piv expression was thermoregulated at stationary phase, but not exponential phase, and that piv is thermoregulated at the level of transcription. Protein levels of known transcriptional regulators of piv, the quorum sensing regulator LasR and the gene-silencing histone nucleoid silencing proteins MvaT/MvaU, were not thermoregulated. Using a transcriptional reporter for piv, we show that LasR activates piv expression at stationary phase at 25°C but not 37°C, while MvaT/MvaU are not required for piv thermoregulation. We also identified a las box in the piv promoter, which is important for piv thermoregulation. We propose that LasR directly regulates piv at stationary phase at 25°C but has a negligible impact at 37°C. Here, we show that piv is uniquely regulated by LasR in a temperature-dependent manner. Our findings suggest that the LasRI quorum sensing regulon of P. aeruginosa may not be fully characterized and that growth at non-standard laboratory conditions such as lower temperatures could reveal previously unrecognized quorum sensing regulated genes.

Imaging of Central Nervous System Infections in the Immunocompromised Patient

Immunocompromised patients are susceptible to the same infections as immunocompetent individuals and have an additional unique risk for atypical infections in the central nervous system (CNS). Many CNS infections carry a poor prognosis if not treated promptly, so it is prudent for radiologists to recognize key findings and have a high level of suspicion in immunocompromised patients. Moreover, a patient may have no known deficiency but can present with an atypical CNS infection as their first sign of an immunocompromised state, thus allowing the radiologist to be the first to suggest specific workup such as HIV testing. Because different infection sources (bacterial, fungal, and parasitic) have separate treatments, it is highly valuable to guide management in the right direction early in the diagnostic workup. This article discusses common opportunistic infections observed in the immunocompromised patient, primarily focusing on neuroimaging findings and pertinent clinical background and treatment for each disease entity. This article also emphasizes the importance of familiarity with the differential diagnosis for ring-enhancing lesions within the CNS.

Viral Infection in Upper Gastrointestinal Tract

Viral infections of the upper gastrointestinal (GI) tract are not uncommon in clinical practice; however, these are frequently observed in immunocompromised patients and rarely in immunocompetent hosts. Compared with esophagitis, which may be associated with clinically significant outcomes, the stomach is a relatively rare site for opportunistic infections in immunocompetent patients. The most common clinically relevant upper GI tract viral infections include cytomegalovirus (CMV), Epstein-Barr virus (EBV), and herpes simplex virus infections. CMV esophagitis and gastritis, which primarily occur in immunocompromised patients, necessitate antiviral treatment, whereas immunocompetent patients typically respond to proton pump inhibitor administration. Most EBV-induced gastric infections are asymptomatic. However, EBV infection is a known etiological contributor to stomach cancer. EBV-associated gastric cancer shows distinctive clinical, pathological, genetic, and post-genetic mutation features and is therefore a clinically significant entity. Herpetic esophagitis usually affects immunocompromised patients and is uncommon in immunocompetent individuals. In this review, we discuss the general aspects and recent studies that have reported esophageal and gastric infections in immunocompromised patients.

Mycoplasma hominis Pneumonia Presented as a Cavitary Mass with a Halo Sign in an Immunocompetent Adult Male: A Case Report

Abstract Mycoplasma hominis is an opportunistic microorganism that colonizes the genitourinary tract and causes genitourinary infections. However, pulmonary infections caused by M. hominis have rarely been reported in immunocompetent individuals. Herein, we report a rare case of an immunocompetent adult male with M. hominis pneumonia who presented with multiple pulmonary nodules that progressed to a cavitary mass with a halo sign. The presence of M. hominis infection was confirmed using multiplex polymerase chain reaction (mPCR) of the bronchoalveolar lavage fluid. The patient demonstrated no response to the initial levofloxacin therapy; however, the symptoms subsequently improved after the administration of moxifloxacin. M. hominis may be an underestimated causative agent of community-acquired pneumonia of unknown etiology in immunocompetent adults, and the involvement of the organism should be especially suspected in sexually active patients. Molecular diagnostic methods, such as mPCR, can be used to identify the etiology of atypical pneumonia. Appropriate antibiotics are crucial for effective treatment.

Flow Cytometry as the Tool to Define Peripheral Blood Leukocyte Signatures in Acute EBV Infection.

Primary Epstein-Barr virus (EBV) infection which can manifest as infectious mononucleosis (IM) is commonly acquired during childhood. EBV primarily invades B cells leading to a lytic reaction; the control of the infection is handled by natural killer and T cells in immunocompetent individuals. The infection has a wide spectrum of clinical findings and can lead to serious complications in patients with certain underlying immunological dysfunctions. We retrospectively investigated peripheral white blood cell populations' surface marker characteristics in IM using a comprehensive flow cytometry marker panel. Twenty-one cases of IM and seventeen EBV-seropositive cases without IM serving as controls were included. We observed novel alterations in lymphocyte, neutrophil, and monocyte populations. In addition to increased activated cytotoxic T cells and low B cells, we demonstrated high T-large granular lymphocyte (T-LGL) populations in IM cases. Furthermore, despite T cells' increased HLA-DR expression, another activation marker, CD11b, was lower in T-LGL populations. Monocytes showed increased CD16 expression; CD64 was higher in neutrophils. Our findings point to monocyte and neutrophil activation which may account for acute clinical features and may contribute to the understanding of IM immunobiology. Furthermore, they may serve as a useful tool in investigating inherited and post-transplant conditions characterized by deficiencies in controlling EBV infection.

Tsukamurella Bacteremia in a Surgical Patient: Case Report and Review of the Literature.

Background: Tsukamurella species were first isolated in 1941. Since then, 48 cases of Tsukamurella bacteremia have been reported, a majority of which were immunosuppressed patients with central venous catheters.A case is described and previous cases of Tsukamurella bacteremia are reviewed. Patients and Methods: A 70-year-old total parenteral nutrition (TPN)-dependent female with recurrent enterocutaneous fistula (ECF), developed leukocytosis one week after a challenging ECF takedown. After starting broad-spectrum antibiotic agents, undergoing percutaneous drainage of intra-abdominal abscess, and subsequent repositioning of the drain, her leukocytosis resolved. Blood and peripherally inserted central catheter (PICC) cultures grew Tsukamurella spp. The patient was discharged to home with 14 days of daily 2 g ceftriaxone, with resolution of bacteremia. Conclusions: Tsukamurella spp. are a rare opportunistic pathogen predominantly affecting immunocompromised patients, with central venous catheters present in most cases. However, there have been few reported cases in immunocompetent individuals with predisposing conditions such as end-stage renal disease and uncontrolled diabetes mellitus.

Porcine model ofacomplicated skin and soft tissue infection caused byPseudomonas aeruginosa.

Pseudomonas aeruginosa poses asignificant threat toboth immunocompetent and immunocompromised individuals, often resulting inlife-threatening infections. With increasing antimicrobial resistance, novel therapeutic strategies are urgently needed. Although animal models are crucial for preclinical studies, limited data are available for porcine models, more specifically for P.aeruginosa complicated skin and soft tissue infections (cSSTIs). This study presents anovel porcine model inducing and sustaining cSSTI for 14days. Six pigs (120wounds) were used for the development ofinfections, and within this group, two pigs (40wounds) were used toevaluate the progression ofthe cSSTI infection. The model demonstrated bacterial loads ofmore than 107CFU/gram oftissue orhigher. The cSSTI fully developed within three days and remained well above these levels until day 14post-infection. Due tothe immunocompetence ofthis model, all the immunological processes associated with the response tothe presence ofinfection and the wound healing process are preserved.

Mucosal emphysematous head and neck infections: Scoping review and a case of emphysematous tonsillitis.

This scoping review seeks to understand the existing research in otolaryngological mucosal emphysematous infections and to elucidate gaps in knowledge in the field. We also present a case of bilateral necrotizing tonsillitis in an immunocompromised patient with the first reported imaging findings of emphysematous abscess of the tonsils. PubMed, Embase, Web of Science. We conducted our review according to the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews. Patient presentation, management, and outcomes were summarized. We also describe the case of a patient with aplastic anemia found to have emphysematous tonsillitis, managed with intubation, broad spectrum intravenous antibiotics and bilateral tonsillectomy. We identified seven case reports or series, involving nine total patients, who presented with emphysematous epiglottitis, supraglottitis, or tonsillitis. The hallmark imaging characteristic was submucosal "gas bubble" on computed tomography. Presenting symptoms included dysphagia, odynophagia, dysphonia, cough, and fever. Both immunocompetent and immunocompromised patients were affected. All patients were treated with broad spectrum antibiotics, and most with steroids. Patients at risk of airway compromise also underwent intubation and surgical drainage or debridement of the emphysematous infection. Emphysematous pharyngeal infections are rare but potentially life-threatening infections that can progress rapidly, resulting in airway compromise and sepsis in both immunocompetent and immunocompromised individuals. We highlight the importance of swift intervention, with intubation and surgical intervention often required for severe cases. More research is needed on common pathogens and patient risk factors to guide future medical and surgical management.

Increased Risk of Herpes Zoster in Rheumatoid Arthritis Not Only Due to JAK Inhibitors-Study of 392 Patients from Single University Center.

Background/Objectives: Patients with rheumatoid arthritis (RA) have an increased risk of infection. Their risk of presenting herpes zoster (HZ) is 1.5-2 times higher than immunocompetent individuals and disseminated presentation is more frequent. Our aim was to analyze the prevalence and general features of HZ in RA patients. Methods: This was a prospective study of 392 RA patients included in the vaccination program of our hospital between 2011 and 2016, and follow-up continued until December 2020. A diagnosis of HZ was made according to clinical manifestations: skin rash, blisters, paresthesia, and local pain in one or more dermatomes. Results: We studied 392 participants (309 women/83 men), mean age 59 ± 13 years. Every patient was followed-up over a mean period of 137 ± 110 months (range: 42 months-42 years). HZ infection was observed in 30 of 392 (25 women/5 men) patients, age (mean ± SD) 64.7 ± 11.8 years. Prevalence was 7.65% in this period and the incidence rate was 13.22/1000 patients/year. Three patients had facial involvement, one had optic involvement, and one patient presented disseminated HZ. Seven patients presented post herpetic neuralgia treated with gabapentinoids. The main features of RA of these 30 patients were: positive RF (n = 17; 56.6%), positive anti-CCP (n = 13; 43.3%), and erosive disease (n = 10; 33.3%). At HZ infection, the treatments were glucocorticoids (n = 19; 63.3%), conventional DMARDs (n = 15; 50%), biological DMARDs (n = 15; 50%), tofacitinib (n = 2; 6.6%), and upadacitinib (n = 1; 3.3%). Conclusions: HZ is a relatively frequent viral complication in RA patients. In our series, one patient presented disseminated HZ and nearly 25% of patients had post-herpetic neuralgia. Including a HZ vaccine in our vaccination program for RA patients may be beneficial.

Plasmablastic lymphoma: 2024 update on diagnosis, risk stratification, and management.

Plasmablastic lymphoma (PBL) is a rare CD20-negative aggressive lymphoma with a poor prognosis under standard treatment options. Though PBL is associated with human immunodeficiency virus infection and other immunosuppressed states, it can also affect immunocompetent individuals. The diagnosis requires a high clinical suspicion and pathological confirmation. EBER expression and MYC gene rearrangements are frequently detected. The differential diagnosis includes EBV+ diffuse large B-cell lymphoma, extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B-cell lymphoma, among others. Age ≥60 years, advanced clinical stage, and high intermediate and high International Prognostic Index scores are associated with worse survival. Combination chemotherapy regimens, such as EPOCH, are recommended. The addition of bortezomib, lenalidomide, or daratumumab might improve outcomes. Including PBL patients and their participation in prospective clinical trials is warranted.

In Vitro Evaluation of Anti-Parasitic Activities of Quinolone-Coumarin Hybrids Derived from Fluoroquinolones and Novobiocin Against Toxoplasma gondii.

Toxoplasmosis is caused by the parasite Toxoplasma gondii (T. gondii). In immunocompetent individuals, the infection is often asymptomatic; however, in expectant mothers and those with immune system deficiencies, complications may arise. Consequently, there is a need for new drugs that cause minimal damage to host cells. The purpose of this study was to investigate the in vitro antiparasitic efficacy of quinolone-coumarin hybrids QC1-QC12, derived from quinolone antibacterials and novobiocin, against T. gondii. The derivatives were compared with novobiocin and ciprofloxacin during testing, with pyrimethamine used as a positive control. We conducted the MTT assay to examine the anti-toxoplasmic effects of the test compounds and novobiocin. Evaluation included the infection and proliferation indices, as well as the size and number of plaques, based on the viability of both healthy and infected cells. The in vitro assays revealed that QC1, QC3, QC6, and novobiocin, with selectivity indices (SIs) of 7.27, 13.43, and 8.23, respectively, had the least toxic effect on healthy cells and the highest effect on infected cells compared to pyrimethamine (SI = 3.05). Compared to pyrimethamine, QC1, QC3, QC6, and novobiocin Without having a significant effect on cell viability, demonstrated a significant effect on reducing in both infection index and proliferation index, in addition to reducing the quantity and dimensions of plaques ( P < 0.05). Based on our results, QC1, QC3, QC6, and novobiocin due to their significant therapeutic effects could be considered as potential new leads in the development of novel anti-Toxoplasma agents.

Characteristics of culture-negative subclinical pulmonarytuberculosis: a single-center observation.

Little is known about culture-negative subclinical pulmonary tuberculosis (TB), and its diagnosis remains challenging. Therefore, this study aimed to identify the characteristics and the extent of disease associated with culture-negative subclinical pulmonary TB. This retrospective cohort study was conducted on immunocompetent individuals with subclinical pulmonary TB at a university hospital in Thailand from January 2014 to December 2019. Subclinical pulmonary TB was diagnosed based on the presence of radiographic abnormalities consistent with TB in the absence of TB symptoms. All subjects demonstrated significant improvement or resolution of radiographic abnormalities following the completion of treatment. At least two negative sputum cultures were needed to fulfill the definition of culture-negative pulmonary TB. Data were analyzed using univariate and multiple logistic regression analyses to determine the characteristics of those with culture-negative subclinical pulmonary TB compared to culture-positive ones. Out of the 106 individuals identified with subclinical pulmonary TB, 84 met the criteria for inclusion in the analysis. The study found lower radiographic extent and increasing age were key attributes of culture-negative subclinical pulmonary TB. The odds ratios (95% confidence interval) were 7.18 (1.76 to 29.35) and 1.07 (1.01 to 1.13), respectively. They tend to have lower rates of bilateral involvement in both chest x-ray (8.5% vs. 32.0%, p=0.006) and computed tomography (15.4% vs. 42.9%, p=0.035). However, no other specific radiographic findings were identified. People with culture-negative subclinical pulmonary TB were likely to have less radiographic -severity, reflecting early disease. Nevertheless, no radiographic patterns, except for unilaterality, were related to culture-negative subclinical pulmonary TB.

SARS-CoV-2-Specific Antibodies, B Cell and T Cell Immune Responses after ChAdOx1 nCoV-19 Vaccination in Solid Organ Transplant Recipients.

Immunization against SARS-CoV-2 is essential for vulnerable solid organ transplant (SOT) recipients who are at risk of infection. However, there are concerns about suboptimal immunogenicity, especially in humoral immunity (HMI), and limited exploration of cell-mediated immune (CMI) responses. The primary objective of this study was to assess the immunogenicity of ChAdOx1 nCoV-19 vaccination in SOT recipients. The secondary endpoint was to evaluate factors that affect immunogenicity and adverse events (AEs) following immunization in SOT recipients. All adult SOT recipients who received the two-dose ChAdOx1 nCoV-19 vaccine at a 12-week interval underwent measurements of HMI by evaluating anti-receptor-binding domain (RBD) IgG levels and CMI by investigating SARS-CoV-2-specific T cell and B cell responses before and after complete vaccination, around 2-4 weeks post-vaccination, and compared to controls. AEs were monitored in all participants. The study included 63 SOT recipients: 44 kidney recipients, 16 liver recipients, and 3 heart transplant recipients, along with 11 immunocompetent controls. Among SOT recipients, 36% were female, and the median (IQR) age was 52 (42-61). The median (IQR) time since transplant was 55 (28-123) months. After the second dose, the median (IQR) anti-RBD antibody levels were significantly lower in SOT recipients compared to those in the control group (8.3 [0.4-46.0] vs. 272.2 [178.1-551.6] BAU/mL, p < 0.01). This resulted in a seroconversion rate (anti-RBD antibody > 7.1 BAU/mL) of 51% among SOT recipients and 100% among controls (p = 0.008). Receiving the vaccine beyond one year post-transplant significantly affected seroconversion (OR 9.04, 95% CI 1.04-78.56, p = 0.046), and low-dose mycophenolic acid marginally affected seroconversion (OR 2.67, 95% CI 0.89-7.96, p = 0.079). RBD-specific B cell responses were also significantly lower compared to those in the control group (0 [0-4] vs. 10 [6-22] SFUs/106 PBMCs, p = 0.001). Similarly, S1- and SNMO-specific T cell responses were significantly lower compared to those in the control group (48 [16-128] vs. 216 [132-356] SFUs/106 PBMCs, p = 0.004 and 20 [4-48] vs. 92 [72-320] SFUs/106 PBMCs, p = 0.004). AEs were generally mild and spontaneously resolved. SOT recipients who received the full two-dose ChAdOx1 nCoV-19 vaccine demonstrated significantly diminished HMI and CMI responses compared to immunocompetent individuals. Consideration should be given to administering additional vaccine doses or optimizing immunosuppressant regimens during vaccination (Thai Clinical Trial Registry: TCTR20210523002).

Global Burden and Evolving Understanding of Hepatitis E Virus

Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis worldwide, recognized as a significant global public health concern. Recent advancements in understanding the natural history of HEV infection have shed light on its epidemiology and clinical implications. The primary mode of HEV transmission is fecal-oral, occurring through contaminated water or food. Parenteral transmission, particularly through blood transfusions, was initially overlooked but has been increasingly recognized in both developing and industrialized countries. Acute HEV infection typically manifests as self-limiting jaundice, particularly in immunocompetent individuals. However, recent data suggest that acute infection can progress to a chronic form in various immunosuppressive conditions, including solid organ transplantation, hematological malignancies, and human immunodeficiency virus (HIV) infection. Chronic HEV can lead to cirrhosis, which may progress rapidly in some cases. Extrahepatic manifestations, particularly neurological complications, have also been reported. HEV remains underdiagnosed globally due to a lack of awareness among healthcare providers in many regions. Advances in serological and molecular assays have facilitated reliable diagnosis, both in immunocompetent and immunocompromised patients. Ribavirin monotherapy has proven effective in treating chronic HEV infection in immunosuppressed individuals and is currently widely recommended. However, its efficacy in acute HEV remains inconclusive. In 2011, an effective and well-tolerated HEV vaccine was developed and approved in China. This vaccine holds promise for high-risk populations, particularly individuals with cirrhosis and travelers to endemic regions.

The role of microRNA-142a in Toxoplasma gondii infection-induced downregulation of Foxp3: implications for adverse pregnancy outcomes

BackgroundToxoplasma gondii (T. gondii) is capable of infecting nearly all warm-blooded animals and approximately 30% of the global population. Though most infections are subclinical in immunocompetent individuals, congenital contraction can lead to severe consequences such as spontaneous abortion, stillbirth, and a range of cranio-cerebral and/or ocular abnormalities. Previous studies reported that T. gondii-infected pregnancy mice unveiled a deficit in both the amount and suppressive functions of regulatory T (Treg) cells, accompanied with reduced levels of forkhead box p3 (Foxp3). Recently, accumulative studies have demonstrated that microRNAs (miRNAs) are, to some extent, relevant to T. gondii infection. However, the link between alterations in miRNAs and downregulation of Foxp3 triggered by T. gondii has been only sporadically studied.MethodsQuantitative reverse transcription polymerase chain reaction (RT-qPCR), protein blotting and immunofluorescence were employed to evaluate the impact of T. gondii infection and antigens on miRNA transcription and Foxp3 expression. Dual-luciferase reporter gene assays were performed to examine the fluorescence activity in EL4 cells, which were transfected with recombinant plasmids containing full-length/truncated/mutant microRNA-142a-3p (miR-142a) promoter sequence or wild type/mutant of Foxp3 3’ untranslated region (3’ UTR).ResultsWe found a pronounced increase in miR-142a transcription, concurrent with a decrease in Foxp3 expression in T. gondii-infected mouse placental tissue. Similarly, comparable findings have been experimentally confirmed through the treatment of EL4 cells with T. gondii antigens (TgAg) in vitro. Simultaneously, miR-142a mimics attenuated Foxp3 expression, whereas its inhibitors markedly augmented Foxp3 expression. miR-142a promoter activity was elevated upon the stimulation of T. gondii antigens, which mitigated co-transfection of mutant miR-142a promoter lacking P53 target sites. miR-142a mimics deceased the fluorescence activity of Foxp3 3’ untranslated region (3’ UTR), but it did not affect the fluorescence activity upon the co-transfection of mutant Foxp3 3’ UTR lacking miR-142a target site.ConclusionIn both in vivo and in vitro studies, a negative correlation was discovered between Foxp3 expression and miR-142a transcription. TgAg enhanced miR-142a promoter activity to facilitate miR-142a transcription through a P53-dependent mechanism. Furthermore, miR-142a directly targeted Foxp3 3’ UTR, resulting in the downregulation of Foxp3 expression. Therefore, harnessing miR-142a may be a possible therapeutic approach for adverse pregnancy caused by immune imbalances, particularly those induced by T. gondii infection.

Toxoplasma gondii infection positively associated with schizophrenia: Evidences from UK Biobank cohort and case-controlled studies

Toxoplasma gondii (T. gondii) is an opportunistic pathogen affecting about 1/3 of world population. While often asymptomatic in immunocompetent individuals, it can lead to severe toxoplasmosis in immunocompromised patients. Recent research has unveiled a potential link between T. gondii infection and neuropsychiatric diseases. We implemented both a cohort study and a case control study to further identify this association. In the cohort study, we analyzed data from the UK Biobank database, which included 8814 individuals tested for T. gondii SAG1 antibodies and free of neuropsychiatric disorders at baseline. Among them, 22.52% (n = 1985) tested positive for SAG1 antibody. Over an average follow-up period of 12.26 years, Cox proportional hazards models and logistic regression analysis revealed a significant association between the SAG1 seropositivity at baseline and the incidence of schizophrenia (HR: 5.89; 95% CI: 1.69–20.53). In our case-control study, 239 patients diagnosed with schizophrenia and 455 healthy individuals were involved. Using the modified agglutination test (MAT) to detect T. gondii antibodies, logistic regression analysis showed a higher prevalence of T. gondii infection among schizophrenia patients (10.04%) compared to healthy controls (3.74%). T. gondii infection emerged as a significant risk factor for schizophrenia (OR: 3.33; 95% CI: 1.68–6.61). However, our investigations did not reveal a robust association between T. gondii infection and other neuropsychiatric conditions, including Alzheimer's disease, dementia, anxiety, depression, neurodegenerative disorders, and peripheral neurological disorders such as neurological and plexus disorders.

Epstein-Barr Virus-Associated Smooth-Muscle Tumor of the Brain.

Epstein-Barr virus, a herpesvirus, has been associated with a variety of cancers, including Burkitt, Hodgkin, and non-Hodgkin lymphomas; posttransplant lymphoproliferative disorders; gastric carcinoma; and nasopharyngeal carcinoma, in both immunocompetent and immunocompromised individuals. Previous studies have established a connection between Epstein-Barr virus and the development of smooth-muscle tumors. Smooth-muscle tumors of the brain are very rare and are often misdiagnosed as meningiomas on imaging. To our knowledge, advanced imaging findings such as MR perfusion of smooth-muscle tumors of the brain have never been reported. We describe the radiologic and pathologic features of the Epstein-Barr virus-associated smooth-muscle tumors of the brain in a person with newly diagnosed advanced HIV.