Initial immune response after exposure to Mycobacterium tuberculosis or to SARS-COV-2: similarities and differences

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) and Coronavirus disease-2019 (COVID-19), whose etiologic agent is severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are currently the two deadliest infectious diseases in humans, which together have caused about more than 11 million deaths worldwide in the past 3 years. TB and COVID-19 share several aspects including the droplet- and aerosol-borne transmissibility, the lungs as primary target, some symptoms, and diagnostic tools. However, these two infectious diseases differ in other aspects as their incubation period, immune cells involved, persistence and the immunopathological response. In this review, we highlight the similarities and differences between TB and COVID-19 focusing on the innate and adaptive immune response induced after the exposure to Mtb and SARS-CoV-2 and the pathological pathways linking the two infections. Moreover, we provide a brief overview of the immune response in case of TB-COVID-19 co-infection highlighting the similarities and differences of each individual infection. A comprehensive understanding of the immune response involved in TB and COVID-19 is of utmost importance for the design of effective therapeutic strategies and vaccines for both diseases

Systemic adipokines, hepatokines and interleukin-6 in HCV-monoinfected and HCV/HIV coinfected patients treated with direct antiviral agents (DAAs)

In this study, we demonstrated that that altered levels ofadipokines/hepatokines in HCV-infected patients, including HIV coinfected, can be restored by treatment with direct antiviral agents (DAAs), thus indicating the important metabolic changes occurring during the eradication of this viral infection

Modulation of tryptophan/serotonin pathway by probiotic supplementation in human immunodeficiency virus-positive patients: preliminary results of a new study approach

Background: To date, no data are available regarding the effects of probiotics on the pathway of tryptophan/serotonin metabolism among human immunodeficiency virus (HIV) 1–infected individuals. Because a condition of dysbiosis might be responsible for the altered use of tryptophan described in this population, the aim of this study was to investigate the link between probiotic supplementation and serotonin levels in combined antiretroviral therapy–treated patients and the subsistence of an interplay with inflammation. Methods: We conducted a pilot study that included 8 HIV-positive subjects. We collected blood and fecal samples before and after 6 months of probiotic supplementation, to measure the level of serotonin in serum and tryptophan in stool, the expression of CD38 and HLADR on peripheral CD4+ T lymphocytes (as immune activation markers), the expression of indoleamine 2,3-dioxygenase 1 messenger RNA (mRNA) and IFN-γ mRNA (as markers of tryptophan metabolism and systemic inflammation). Results: After probiotic supplementation, we observed a significant increase in concentration of serum serotonin (P=.008) and a decreased level of tryptophan in plasma. Moreover, a significant reduction in CD38 and HLA-DR expression on the surface of peripheral CD4+ T cells (P=.008) and a reduced expression of indoleamine 2,3-dioxygenase 1 mRNA on peripheral blood mononuclear cells (P=.04) were observed. Conclusions: Considering that this probiotic (Vivomixx® in EU; Visbiome® in USA) has an influence on tryptophan metabolism, larger studies on this topic are needed

Alternative biomarkers of tuberculosis infection in patients with immune-mediated inflammatory diseases

IntroductionIFN-γ release assays (IGRAs) are one of the referral tests for diagnosing tuberculosis infection (TBI). To improve IGRAs accuracy, several markers have been investigated. Patients with immune-mediated inflammatory diseases (IMID), taking biological drugs, have a higher risk to progress to TB-disease compared to the general population. In several guidelines, annual TBI screening is recommended for patients undergoing biological therapy. Aim of this study was to investigate, within the QuantiFERON-TB-Plus (QFT-Plus) platform, if beside IFN-γ, alternative biomarkers help to diagnose TBI-IMID patients.MethodsWe enrolled 146 subjects: 46 with TB disease, 20 HD, 35 with TBI and 45 with TBI and IMID. Thirteen IMID subjects with a QFT-Plus negative result were diagnosed as TBI based on radiological evidence of TBI. We evaluated the IP-10 level in response to TB1 and TB2 peptides of QFT-Plus assay and we compared these results with the standardized assay based on IFN-γ. Multiplex immune assay was performed on plasma from TB1 and TB2 tubes and results were analyzed by a gradient boosting machine (GBM) as learning technique.ResultsTBI-IMID showed a significant decreased IP-10 level in response to TB1 and TB2 stimulation compared to TBI-NO IMID (p < 0.0001 and p = 0.0002). The TBI-IMID showed a moderate agreement between the IP-10-based assay and QFT-Plus scores. In TBI-IMID, QFT-Plus showed 70% sensitivity for TBI detection whereas the IP-10-based assay reached 61%. Tests combination increased the sensitivity for TBI diagnosis up to 77%. By a GBM, we explored alternative biomarkers for diagnosing TBI in IMID population reaching 89% sensitivity. In particular, the signature based on IL-2, IP-10, and IL-9 detection was associated with TB status (infection/disease). However, by applying the cut-off identified by ROC analysis, comparing TB and TBI with the HD group, within the IMID population, we did not improve the accuracy for TBI-diagnosis. Similarly, this signature did not improve TBI diagnosis in IMID with radiological evidence of TBI but negative QFT-Plus score.DiscussionTo develop alternative strategies for TBI immune-diagnosis, future studies are needed to evaluate the memory response of TBI defined by radiological tools. These results may help in tuberculosis management of patients taking lifelong immune-suppressive drugs

Effectiveness of attributive retraining on epileptic male children’s mental health

Background: Epilepsy is relatively a common neurological disease in childhood. This disorder affects the ability of the children, their performance and their mental health. Purpose: The purpose of this study was to investigate effectiveness of attributive retraining on epileptic children’s mental health. Methods: In this quasi-experimental study a pre-test post-test design with control group was used. From the statistical population of Iran epilepsy association, 30 epileptic children [17 boys and 13 girls] were selected by accessible sampling and were divided in experimental and control group. General health questionnaire [Goldberg and Hiller, 1979] was used in this study. Experimental group were trained during 11 sessions [each session was 45 minutes and two sessions in each week] then the results were analyzed by Multi variable covariance analysis. Results: The results of analysis of covariance showed that physical symptoms, anxiety and insomnia, disorder in social function, depression was reduced significantly [p>0/01] after attribution retraining intervention in comparison with control group. Discussion: It can be concluded that attributive retraining can increase epileptic children’s mental health and it seems that it would be an appropriate intervention for increasing epileptic children’s mental health

Antigen discovery by bioinformatics analysis and peptide microarray for the diagnosis of cystic echinococcosis.

BackgroundCystic echinococcosis (CE), caused by Echinococcus granulosus sensu lato, is a neglected zoonosis. Its diagnosis relies on imaging, supported by serology, while only imaging is useful for staging and follow-up. Since diagnostic tools and expertise are not widely available, new accurate and easily implementable assays for the diagnosis and follow-up of CE are highly needed.Methodology/principal findingsWe aimed to identify new E. granulosus antigens through a bioinformatics selection applied to the parasite genome, followed by peptide microarray screening and validation in ELISA, using independent panels of sera from patients with hepatic CE and clinically relevant controls. From 950 proteins selected in silico, 2,379 peptides were evaluated by microarray for IgG reactivity and eight candidates selected for validation. Reactivity to one peptide was significantly higher in the CE group (p = 0.044), but had suboptimal diagnostic accuracy.Conclusions/significanceHere we performed bioinformatics analysis and peptide microarray for antigen discovery, useful for the diagnosis of CE. Eight candidates were selected and validated. Reactivity to one peptide associated to CE but had suboptimal diagnostic accuracy. Importantly, the database developed in this study may be used to identify other antigenic candidates for CE diagnosis and follow-up

Exploratory analysis to identify the best antigen and the best immune biomarkers to study SARS-CoV-2 infection

10.1186/s12967-021-02938-8Journal of Translational Medicine19127

Impact of High-Dose Multi-Strain Probiotic Supplementation on Neurocognitive Performance and Central Nervous System Immune Activation of HIV-1 Infected Individuals

Gut microbiota has metabolic activity which influences mucosal homeostasis, local and systemic immune responses, and other anatomical systems (i.e., brain). The effects of dysbiosis are still poorly studied in Human Immunodeficiency Virus-1 (HIV-1) positive subjects and insufficient data are available on the impairment of the gut-brain axis, despite neurocognitive disorders being commonly diagnosed in these patients. This study evaluated the impact of a probiotic supplementation strategy on intrathecal immune activation and cognitive performance in combined antiretroviral therapy (cART) treated HIV-1 infected subjects

Direct-acting antiviral therapy enhances total CD4+ and CD8+ T-cells responses, but does not alter T-cells activation among HCV mono-infected, and HCV/HIV-1 co-infected patients

AIM: Chronic immune activation and poor T-cell immune response are strongly associated with disease progression and pathogenesis of both hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-1 infections. Little is known about the impact of anti-HCV Interferon (IFN)-free direct-acting antiviral (DAA) therapy on the systemic T-cells activation and patterns of peripheral T-cells producing pro-inflammatory cytokines. PATIENTS AND METHODS: Forty-five subjects including 18 HCV mono-infected, 17 HCV/HIV-1 co-infected patients under antiretroviral therapy (ART), and 10 healthy controls (HCs) were recruited. Blood samples were collected at baseline (T0) and 12 weeks after the end of DAA therapy (T1). Cell phenotypes (CD3, CD4, CD8), activation markers (CD38 and HLA-DR), and frequency of IFN-γ, interleukin (IL)-17, and IL-22 producing CD4+ and CD8+ T-cells were measured by flow cytometry. Plasma levels of related cytokines were also measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Both HCV, and HCV/HIV-1 patients before and after therapy, showed significant higher percentages of any T-cell subset expressing CD38 and/or HLA-DR compared to HCs. No differences were observed in T-cells activation at T1 compared to T0 in patient groups, and when HCV patients were compared to HCV/HIV-1 group (P>0.05). After therapy, the potential of total circulating T helper (Th) and T cytotoxic (Tc) cells producing IFN-γ, IL-17, and IL-22 were increased. Plasma level of IFN-γ at baseline was showed difference compared to HCs, and significantly reduced after therapy (P<0.05). CONCLUSION: Total T-cells immune response enhances after therapy, however, the state of immune activation may remain elevated for a longtime after the end of treatment and contribute to post-Sustained Virologic Response (SVR) consequences

Direct-acting antiviral therapy enhances total CD4+ and CD8+ T-cells responses, but does not alter T-cells activation among HCV mono-infected, and HCV/HIV-1 co-infected patients

AIM: Chronic immune activation and poor T-cell immune response are strongly associated with disease progression and pathogenesis of both hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-1 infections. Little is known about the impact of anti-HCV Interferon (IFN)-free direct-acting antiviral (DAA) therapy on the systemic T-cells activation and patterns of peripheral T-cells producing pro-inflammatory cytokines. PATIENTS AND METHODS: Forty-five subjects including 18 HCV mono-infected, 17 HCV/HIV-1 co-infected patients under antiretroviral therapy (ART), and 10 healthy controls (HCs) were recruited. Blood samples were collected at baseline (T0) and 12 weeks after the end of DAA therapy (T1). Cell phenotypes (CD3, CD4, CD8), activation markers (CD38 and HLA-DR), and frequency of IFN-γ, interleukin (IL)-17, and IL-22 producing CD4+ and CD8+ T-cells were measured by flow cytometry. Plasma levels of related cytokines were also measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Both HCV, and HCV/HIV-1 patients before and after therapy, showed significant higher percentages of any T-cell subset expressing CD38 and/or HLA-DR compared to HCs. No differences were observed in T-cells activation at T1 compared to T0 in patient groups, and when HCV patients were compared to HCV/HIV-1 group (P>0.05). After therapy, the potential of total circulating T helper (Th) and T cytotoxic (Tc) cells producing IFN-γ, IL-17, and IL-22 were increased. Plasma level of IFN-γ at baseline was showed difference compared to HCs, and significantly reduced after therapy (P<0.05). CONCLUSION: Total T-cells immune response enhances after therapy, however, the state of immune activation may remain elevated for a longtime after the end of treatment and contribute to post-Sustained Virologic Response (SVR) consequences