Immune Response In Individuals Research Articles

The role of oral supplementation with immunonutrients in the inflammatory response in patients with COVID-19

Introduction: The SARS-CoV-2 related coronavirus has spread to almost every country, causing the COVID-19. The severity of COVID-19 is based on the inflammation caused by the cytokine storm. Inflammatory markers suggest a molecular explanation for the occurrence of severe disease and represent a possible treatment. Objective: This review aims to analyse the plausibility of using oral supplementation with immunonutrients. Discussion: Immunonutrition studies the interactions between nutrition, the immune system, infection, and inflammation of tissues. Arginine is a fundamental amino acid in processes of metabolic stress. Its deficiency implies in the capacity of immune response. ω-3 fatty acids demonstrated improved lung compliance, oxygenation, mechanical ventilation time and intensive care unit stay in patients with acute respiratory distress syndrome. Essential for cell-mediated immunity and T lymphocyte function, dietary nucleotides have been shown to improve the cytotoxicity of natural killer cells. Considering that the inversely proportional relationship between presence of IL-6 and TNF-α and the function of T cells is well established in patients with COVID-19, this reinforces the idea that the release control of these biomarkers can be a way to treat this disease. Conclusion: In this scenario, this review raises the possibility of using immunonutrition to improve immune response of individuals affected by COVID-19.

Treg and TH17 link to immune response in individuals with peri-implantitis: a preliminary report.

Treg and TH17 cells influence the inflammatory process in periodontal diseases and could also play in a similar pattern, an essential role in immune-inflammatory mechanisms involved in the destruction of the peri-implant tissues, peri-implantitis. Therefore, this study evaluated the levels of RORγT and FOXP3 gene expression in subjects with peri-implantitis and healthy peri-implant tissues. A total of 35 subjects with implant-supported restorations in both diseased and healthy clinical conditions (n = 15 healthy; n = 20 peri-implantitis) were included in this study. Peri-implantitis was defined as probing depth > 5 mm, bleeding on probing and/or suppuration, and peri-implant bone loss >4 mm. Peri-implant tissue biopsies were collected for analysis of the mRNA, RORγT, and FOXP3 expression levels. The samples were submitted to total RNA extraction, treatment with DNAse, and cDNA synthesis. Subsequently, real-time PCR reaction was performed to evaluate the levels of RORγT and FOXP3 gene expression to the reference gene. These were analyzed by the non-parametric Mann-Whitney method with a level of significance of 5%. Higher gene expression levels of the transcription factors RORγT and FOXP3 were detected in the tissues affected by peri-implantitis when compared with healthy tissues (p < 0.05). The present study demonstrated the possible existence of a hybrid TH17-Treg profile, based on the gene expression of transcription factors inducing differentiation of these cells. Further studies must be designed to gain a better understanding of the immunological mechanisms involved in the pathogenesis of peri-implantitis. The levels of RORγT and FOXP3 transcription factors that were linked to cells with the FOXP3+RORγT+ phenotype could be used as a predictor of peri-implantitis progression.

Lower influenza-specific cell-mediated immune responses in individuals with atopic dermatitis compared with healthy controls

ABSTRACT In a sub-study of a clinical trial (NCT01737710) investigating the immunogenicity of trivalent inactivated influenza vaccine (IIV3) administered intradermally or intramuscularly to individuals with atopic dermatitis (AD), we assessed T cell and antigen-presenting cell (APC) responses to influenza B in AD and Non-AD controls. The comparison of IFN-γ ELISpot in 58 AD and 31 Non-AD showed lower responses in AD pre-vaccination. Pre-vaccination, AD also had lower Th2 responses and less inflammatory cytokine production by APC measured by flow cytometry and cytokine levels in culture supernatants. AD also had lower Th1 and Th2 responses to nonspecific anti-CD3/anti-CD28-stimulation, but these were not significantly correlated with the influenza-specific responses, suggesting a primary role for the APC in the decreased influenza-specific T cell responses. Multivariate modeling of influenza-specific responses pre-vaccination with influenza-specific antibody titers and IFN-γ ELISpot as outcome measures identified several T cell and APC subsets that negatively or positively predicted protective responses to the vaccine. However, none of the functional differences between AD and Non-AD had high predictive value on adaptive responses to influenza vaccine, which was in agreement with the overall similar responses to the vaccine in the parent clinical trial.

8 ROLE OF THE HOST IMMUNE RESPONSE TO ENTERIC PROKARYOTIC VIRUSES IN INFLAMMATORY BOWEL DISEASE

Gut microbiota comprise important environmental exposures that influence human immune systems and may alter the clinical course of inflammatory bowel disease (IBD). Little is known about the role of gut bacteriophages (viral components that infect prokaryotic bacteria) and their interactions with the host’s immune responses. We tested the hypotheses that (1) immune responses of individuals with IBD to phages differ from those without IBD and (2) immune responses to phages are associated with disease type (i.e. those with Crohn’s disease have different responses than those with ulcerative colitis).

8 ROLE OF THE HOST IMMUNE RESPONSE TO ENTERIC PROKARYOTIC VIRUSES IN INFLAMMATORY BOWEL DISEASE

Abstract Background Gut microbiota comprise important environmental exposures that influence human immune systems and may alter the clinical course of inflammatory bowel disease (IBD). Little is known about the role of gut bacteriophages (viral components that infect prokaryotic bacteria) and their interactions with the host’s immune responses. We tested the hypotheses that (1) immune responses of individuals with IBD to phages differ from those without IBD and (2) immune responses to phages are associated with disease type (i.e. those with Crohn’s disease have different responses than those with ulcerative colitis). Methods We have constructed the first bacteriophage peptidome library (“phageome”), based on sequencing of environmental phages and large-scale metagenomic sequencing of virus-like particles isolated from stool samples from IBD patients and their non-IBD household contacts. Using Phage ImmunoPrecipitation Sequencing (PhIP-Seq) technology, we generated complete serum antibody binding profiles of 48 IBD patients (16 ulcerative colitis, 11 Crohn’s, and 11 indeterminate), 9 of their non-IBD household contacts, and an independent non-IBD cohort of 674 volunteers collected by the Vaccine Research Center (VRC) at the National Institutes of Health. Antibody binding profiles were compared among groups using nonparametric statistics. Results IBD patients as a group had lower antibody responses to specific phages compared to both non-IBD household contacts and the non-IBD VRC controls; this difference was significant and remained after control for unequal sample sizes [Figure 1]. Patients with Crohn’s disease compared to those with ulcerative colitis had similar antibody responses. Particularly for phages of the genera Phifelvirus, the immune responses of Crohn’s patients were significantly reduced compared to their non-IBD household contacts, while the immune responses of patients with ulcerative colitis did not significantly differ from non-IBD household contacts [Figure 2]. IBD disease type comparisons to the VRC controls yielded similar results. Conclusion PhIP-Seq with a phageome library can be used to study the relationship between immune responses and gut bacteriophages in IBD. Our results suggest that IBD patients may have lower antibody responses to specific phages compared to non-IBD individuals. Differential antibody reactivities in Crohn’s disease vs. ulcerative colitis compared to their household contacts and VRC controls suggest disease-specific response to the gut phageome that warrant further study.

Influenza-specific IgG1+ memory B-cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency.

BackgroundAnnual influenza vaccination is recommended to all individuals over 6 months of age, including predominantly antibody deficiency (PAD) patients. Vaccination responses are typically evaluated by serology, and because PAD patients are by definition impaired in generating IgG and receive immunoglobulin replacement therapy (IgRT), it remains unclear whether they can mount an antigen‐specific response.ObjectiveTo quantify and characterise the antigen‐specific memory B (Bmem) cell compartment in healthy controls and PAD patients following an influenza booster vaccination.MethodsRecombinant hemagglutinin (HA) from the A/Michigan/2015 H1N1 (AM15) strain with an AviTag was generated in a mammalian cell line, and following targeted biotinylation, was tetramerised with BUV395 or BUV737 streptavidin conjugates. Multicolour flow cytometry was applied on blood samples before and 28 days after booster influenza vaccination in 16 healthy controls and five PAD patients with circulating Bmem cells.ResultsRecombinant HA tetramers were specifically recognised by 0.5–1% of B cells in previously vaccinated healthy adults. HA‐specific Bmem cell numbers were significantly increased following booster vaccination and predominantly expressed IgG1. Similarly, PAD patients carried HA‐specific Bmem cells, predominantly expressing IgG1. However, these numbers were lower than in controls and did not increase following booster vaccination.ConclusionWe have successfully identified AM15‐specific Bmem cells in healthy controls and PAD patients. The presence of antigen‐specific Bmem cells could offer an additional diagnostic tool to aid in the clinical diagnosis of PAD. Furthermore, alterations in the number or immunophenotype of HA‐specific Bmem cells post‐booster vaccination could assist in the evaluation of immune responses in individuals receiving IgRT.

Effect of Prebiotic, Probiotic, and Enzyme Supplementation on Gut Fermentation, Markers of Inflammation and Immune Response in Individuals with GI Symptoms (P20-024-19)

ObjectivesChronic gastrointestinal distress (GID) effects up to 33.8% of people and results in over 15 million outpatient visits in the US annually. Currently, probiotic and prebiotic supplements are recommended by physicians, dietitians, and other healthcare providers to normalize GI function and to mitigate symptoms associated with certain disease states. GlutenShield (GS) is a commercially available nutritional supplement designed to contain an appropriate balance of pre- and probiotics as well as digestive enzymes to improve symptoms associated with GID. The aim of this study was to determine the tolerance to and/or benefits of GS supplementation on adults with GID. MethodsThis was a partially blinded pilot study in which all subjects completed a 2-week washout and were then randomized to receive GS or the placebo 3 times/day with meals. Participants completed a pre-treatment FFQ as well as a pre- and post-treatment GID questionnaire, POMS questionnaire, blood draw, and stool sample. ResultsNo differences between placebo and treatment groups were found for serum inflammatory cytokines or fecal volatile fatty acids (area % or concentration) (P > 0.05). A significant reduction in IgG2 was observed in the GS group (7110.4 vs 4185.56; P = 0.008) as well as a significant reduction in self-reported bloating (P = 0.038) and approaching significant reduction in total GID (P = 0.083). Fecal insoluble dietary fiber (IDF) percentage significantly increased in the placebo group (P = 0.012), with no change in the GS group (P > 0.05). ConclusionsResearch findings suggest that GS was well tolerated and perceived to be beneficial compared to placebo; however, further research is needed to identify the specific patient population of GID patients who could most benefit from GS supplementation. Future analysis of microbiome data of subjects could provide additional insight. Clinical trial ID: NCT03403387. Funding SourcesETSU (CCRHS, Dean’s Research Enhancement Award and CPH, Health Sciences Funding) and Shield Nutraceuticals, LLC.

Prevalence of specific immunoglobulin E and G against Aspergillus fumigatus in patients with asthma.

Background and Purpose: Aspergillus fumigatus as a ubiquitous fungus can be found in the respiratory tract of the asthmatic and healthy people. The inhalation of Aspergillus spores leads to an immune response in individuals with asthma and results in the aggravation of the clinical symptoms. The present study aimed to investigate the prevalence of specific immunoglobulin E and G (IgE and IgG) against A.fumigatus in asthmatic patients.Materials and Methods:This study was conducted on 200 consecutive patients with moderate to severe asthma referring to Masih Daneshvari hospital Tehran, Iran, from January 2016 to February 2018. Skin prick test (SPT) was performed in all subjects with Aspergillus allergens. Moreover, all patients underwent specific IgE testing for Aspergillus using Hycor method. Enzyme immune assay was applied to measure total IgE and Aspergillus-specific IgG.Results:According to the results, the mean age of the patients was 45.8 years (age range: 18-78 years). The mean levels of total IgE and Aspergillus specific IgE in asthmatic patients were obtained as 316.3 (range: 6-1300 IU/ml) and 1.5 (range: 0.1-61.3 IU/ml), respectively. Out of 200 patients, 27 (13.5%), 65 (32.5%), 22 (11.0%), and 86 (43.0%) cases had positive Aspergillus SPT, total IgE of > 417 IU/ml, Aspergillus-specific IgE, and IgG, respectively. The level of these variables in patients with severe asthma were 16 (16.5%), 36 (37.1%), 15 (15.5%), and 46 (47.4%), respectively.Conclusion:As the findings indicated, reactivity to Aspergillus is a remarkable phenomenon in asthmatic patients. It is also emphasised that the climatic condition may affect the positive rate of hypersensitivity to Aspergillus.

A modified anthrax toxin-based enzyme-linked immunospot assay reveals robust T cell responses in symptomatic and asymptomatic Ebola virus exposed individuals.

BackgroundEbola virus (EBOV) caused more than 11,000 deaths during the 2013–2016 epidemic in West Africa without approved vaccines or immunotherapeutics. Despite its high lethality in some individuals, EBOV infection can produce little to no symptoms in others. A better understanding of the immune responses in individuals who experienced minimally symptomatic and asymptomatic infection could aid the development of more effective vaccines and antivirals against EBOV and related filoviruses.Methodology/Principle findingsBetween August and November 2017, blood samples were collected from 19 study participants in Lagos, Nigeria, including 3 Ebola virus disease (EVD) survivors, 10 individuals with documented close contact with symptomatic EVD patients, and 6 control healthcare workers for a cross-sectional serosurvey and T cell analysis. The Lagos samples, as well as archived serum collected from healthy individuals living in surrounding areas of the 1976 Democratic Republic of Congo (DRC) epidemic, were tested for EBOV IgG using commercial enzyme-linked immunosorbent assays (ELISAs) and Western blots. We detected antibodies in 3 out of 3 Lagos survivors and identified 2 seropositive individuals not known to have ever been infected. Of the DRC samples tested, we detected antibodies in 9 out of 71 (12.7%). To characterize the T cell responses in the Lagos samples, we developed an anthrax toxin-based enzyme-linked immunospot (ELISPOT) assay. The seropositive asymptomatic individuals had T cell responses against EBOV nucleoprotein, matrix protein, and glycoprotein 1 that were stronger in magnitude compared to the survivors.Conclusion/SignificanceOur data provide further evidence of EBOV exposure in individuals without EVD-like illness and, for the first time, demonstrate that these individuals have T cell responses that are stronger in magnitude compared to severe cases. These findings suggest that T cell immunity may protect against severe EVD, which has important implications for vaccine development.

Waterborne Cd2+ weakens the immune responses of blood clam through impacting Ca2+ signaling and Ca2+ related apoptosis pathways

Exposure to heavy metals such as Cadmium (Cd) may exert detrimental impacts on the immune responses of marine bivalve species. However, the immunotoxicity of Cd on blood clams remains unknown to date. Furthermore, though Cd2+ is known to compete with calcium (Ca2+) ions for their binding sites in cells and inhibit Ca2+ influx, whether Cd2+ weakens the immune responses of marine bivalves through inducing intracellular Ca2+ disorders still remains unclear. Therefore, the immunotoxicity of Cd2+ at different waterborne Ca2+ concentrations on blood clam, Tegillarca granosa, were investigated in the present study. Results obtained demonstrated that the total number, phagocytic activity, and red granulocytes ratio of the haemocytes were all significantly reduced after 10 days exposure of individuals to 25 μg/L Cd2+. However, when the waterborne Ca2+ concentrations were elevated by 10% and 20% (approximately 370 and 410 mg/L, respectively), mitigation effects on the immune responses of individuals were detected. In addition, though the expressions of genes from the Ca2+ signaling and Ca2+-related apoptosis pathways were significantly altered by Cd2+ exposure, the expression patterns of these genes were similar to that of the control when the waterborne Ca2+ concentrations were elevated, suggesting a relieving effect of waterborne Ca2+ on Cd2+ induced toxicity to haemocytes. The results obtained in the present study revealed that waterborne Cd2+ may hamper the immune responses of T. granosa through influencing Ca2+ signaling and Ca2+-related apoptosis pathways, which can be partially mitigated by elevating the waterborne Ca2+ concentrations.

A mutation in the progesterone receptor predisposes to HEV infection in HIV-positive patients.

Background and AimsInfection with Hepatitis E virus (HEV) can cause chronic liver disease in immunocompromised hosts. In transplant recipients, the use of certain immunosuppressants and food habits has been proposed as risk factors for HEV. In individuals infected with the human immunodeficiency virus (HIV), risk factors for HEV infection are less clear. We aimed to study the association between a mutation in the progesterone receptor (PR) named PROGINS and HEV‐infected in HIV‐positive individuals.MethodsWe evaluated the presence of the SNP PROGINS via KASP in serum samples of 64 HIV‐positive individuals and 187 healthy controls. We performed ELISA tests to address the serum levels of IL‐10 and IL‐12, as well as T‐cell stimulation assays in peripheral blood to address immune response in individuals with PROGINS.ResultsWe found a significant association between the presence of PROGINS mutation and HEV seroprevalence in individuals infected with HIV (30% in HIV+/HEV+ versus 2% in HIV+/HEV, respectively, P = .009). Moreover, we found that HIV+/HEV+ individuals expressing the PROGINS mutation had lower serum levels of IL‐10 and higher levels of IL‐12. The presence of the mutation led to a reduced response upon stimulation of CD4+ and CD8+ T cells compared to those without the mutation, suggesting an immune modulation associated with PROGINS.ConclusionsOur study identified a mutation in the PR that provides significant insights into mechanisms of HEV infection in immunosuppressed individuals.

Human cellular and humoral immune responses to Phlebotomus papatasi salivary gland antigens in endemic areas differing in prevalence of Leishmania major infection.

BackgroundSand fly saliva compounds are able to elicit specific immune responses that have a significant role in Leishmania parasite establishment and disease outcome. Characterizing anti-saliva immune responses in individuals living in well defined leishmaniasis endemic areas would provide valuable insights regarding their effect on parasite transmission and establishment in humans.Methodology/Principal findingsWe explored the cellular and humoral immune responses to Phlebotomus (P.) papatasi salivary gland extracts (SGE) in individuals living in cutaneous leishmaniasis (CL) old or emerging foci (OF, EF). OF was characterized by a higher infection prevalence as assessed by higher proportions of leishmanin skin test (LST) positive individuals compared to EF. Subjects were further subdivided into healed, asymptomatic or naïve groups. We showed anti-SGE proliferation in less than 30% of the individuals, regardless of the immune status, in both foci. IFN-γ production was higher in OF and only observed in immune individuals from OF and naïve subjects from EF. Although IL-10 was not detected, addition of anti-human IL-10 antibodies revealed an increase in proliferation and IFN-γ production only in individuals from OF. The percentage of seropositive individuals was similar in immune and naïves groups but was significantly higher in OF. No correlation was observed between anti-saliva immune responses and LST response. High anti-SGE-IgG responses were associated with an increased risk of developing ZCL. No differences were observed for anti-SGE humoral or cellular responses among naïve individuals who converted or not their LST response or developed or not ZCL after the transmission season.Conclusions/SignificanceThese data suggest that individuals living in an old focus characterized by a frequent exposure to sand fly bites and a high prevalence of infection, develop higher anti-saliva IgG responses and IFN-γ levels and a skew towards a Th2-type cellular response, probably in favor of parasite establishment, compared to those living in an emerging focus.

HYPERACTIVATION OF PI3 KINASE CAUSES DEFECTS IN HUMAN B-CELL DEVELOPMENT AND DIFFERENTIATION

Abstract Gain of function (GOF) mutations in PIK3CD, encoding the p110δ subunit of PI3-kinase, cause immune dysregulation characterized by recurrent respiratory infections, increased susceptibility to herpesvirus infection, lymphoma, organomegaly and autoimmunity. Affected individuals display poor Ab responses to protein and polysaccharide Ags suggesting defective humoral immune responses. To better understand humoral immune defects due to hyperactive PI3K, we analysed B cells in these individuals. In peripheral blood, transitional B cells were markedly increased while memory B cells were reduced. The phenotype of naïve B cells with PIK3CD GOF mutations resembled that of normal transitional B cells, indicating an aberrant arrest of developing B cells. Analysis of bone marrow revealed increased proportions of pro/pre-B cells and reduced recirculating mature B cells patients with PIK3CD GOF mutations. Within the memory B cell population there was a reduction in IgG+ cells. Consistent with this, there was a selective impairment in IgG production by transitional of naive B cells following in vitro stimulation. To extend these studies in vivo, we generated a mouse model using CRISPR/Cas9 to introduce the common disease-causing mutation (E1021K) into Pik3cd. Analysis of bone marrow from these mice revealed disrupted B-cell development. Investigation of Ag-specific T-dependent B cell responses using mice expressing a transgenic HEL-specific BCR combined with Pik3cd GOF allowed us to dissect defects in specific Ab generation that are seen in human PIK3CD GOF mutations. These results indicate that intrinsic defects in B-cell development and differentiation underlie poor humoral immune responses in individuals with PIK3CD GOF mutations.

HIV Controllers Exhibit Enhanced Frequencies of Major Histocompatibility Complex Class II Tetramer+ Gag-Specific CD4+ T Cells in Chronic Clade C HIV-1 Infection.

Immune control of viral infections is heavily dependent on helper CD4+ T cell function. However, the understanding of the contribution of HIV-specific CD4+ T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4+ T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4+ T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4+ T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4+ T cells in HIV controllers than progressors (P = 0.0001), and these expanded Gag-specific CD4+ T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control (r = -0.5, P = 0.02). These data identify an association between HIV-specific CD4+ T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4+ T cell responses in natural infections.IMPORTANCE Increasing evidence suggests that virus-specific CD4+ T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4+ T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV infections worldwide. Understanding the contribution of HIV-specific CD4+ T cell responses in clade C infection is particularly important for developing vaccines that would be efficacious in sub-Saharan Africa, where clade C infection is dominant. Here, we employed MHC class II tetramers designed to immunodominant Gag epitopes and used them to characterize CD4+ T cell responses in HIV-1 clade C infection. Our results demonstrate an association between the frequency of HIV-specific CD4+ T cell responses targeting an immunodominant DRB1*11-Gag41 complex and HIV control, highlighting the important contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infections.

&amp;lt;i&amp;gt;Schistosoma mansoni&amp;lt;/i&amp;gt; Infection: A Major Contributor of Reduced Effective T Helper Responses against &amp;lt;i&amp;gt;Plasmodium falciparum&amp;lt;/i&amp;gt; and &amp;lt;i&amp;gt;Schistosoma mansoni&amp;lt;/i&amp;gt; Co-Infection in &amp;lt;i&amp;gt;ex vivo&amp;lt;/i&amp;gt;: A Cross-Sectional Study to Assess Th1, Th2 &amp;amp; Th17 Immune Responses

Background: Parasitic worms evade immune responses, and interactions between diseases can cause altered immunologic outcomes compared to what usually occurs with single infections. These interactions may influence vaccine and chemotherapeutic efficacy. Schistosoma mansoni and Plasmodium falciparum are co-endemic in Uganda and are the leading parasitic causes of public health problems across sub-Saharan Africa. Objectives: The overall aim was therefore, to elucidate the impact of S. mansoni infection on protective T helper immune responses on P. falciparum and S. mansoni co-infection. Methodology: This study evaluated the T helper immune responses in individuals with independent S. mansoni infection, independent P. falciparum infection, co-infection and non-infection in school attending children in a co-endemic area along Lake Victoria shores, Uganda. Immune responses were categorized into Th1, Th2, and Th17 based on unique cytokine(s) produced by the T helper subpopulation in ex vivo. Kato Katz thick smears and circulating cathodic antigen tests were performed for S. mansoni screening, whereas thick and thin blood smear techniques were performed for P. falciparum screening. Results: We observed an up regulated Th1 T helper subpopulation in independent P. falciparum infections compared to the uninfected group. Suboptimal T helper immune responses were detected in independent S. mansoni infections characterized by significantly down regulated Th1 (Z = -1.425, p = 0.0313) response in comparison to the non-infected group. Suboptimal T helper immune responses were also recorded in the co-infected individuals characterized by significantly down regulated Th1 (Z = -3.260, p = 0.0273) and Th2 (Z = -1.180, p = 0.0078) responses compared to independent P. falciparum. Conclusions: S. mansoni infection is a major contributor of a reduced effective T helper immune response against P. falciparum in P. falciparum and S. mansoni co-infection.

Suicide attempts and markers of immune response in individuals with serious mental illness

Previous studies have identified elevations in antibodies to Toxoplasma gondii in individuals with a history of suicide attempts but studies have not measured the association between suicide attempts and a panel of antibody markers. We assessed 162 patients receiving treatment for schizophrenia, bipolar disorder, or major depression on the Columbia Suicide Severity Rating Scale for suicide attempt history and other clinical measures. All participants had a blood sample drawn from which were measured antibodies to Toxoplasma gondii and other neurotropic infectious agents. A total of 72 (44%) of participants had a lifetime suicide attempt; these individuals had elevated levels of IgM class antibodies to Toxoplasma gondii and Cytomegalovirus (CMV). We also found an association between the levels of these antibodies and the number of suicide attempts. There was a particularly strong odds of a suicide attempt history in individuals who had elevated levels of IgM antibodies to both Toxoplasma gondii and to CMV suggesting an additive risk associated with the antibodies. These findings remained significant when adjusting for current cigarette smoking and history of drug/alcohol use which were also associated with suicide attempts. We did not find an association between a suicide attempt history and IgG class antibodies to Toxoplasma gondii, CMV, or IgM or IgG antibodies to the Epstein Barr Virus or other antigens tested. The identification of blood-based antibody markers should provide for more personalized methods for the assessment and treatment, and ultimately prevention, of suicide attempts in individuals with serious mental illnesses.

A Frameshift in CSF2RB Predominant Among Ashkenazi Jews Increases Risk for Crohn's Disease and Reduces Monocyte Signaling via GM-CSF

Crohn's disease (CD) has the highest prevalence in Ashkenazi Jewish populations. We sought to identify rare, CD-associated frameshift variants of high functional and statistical effects. We performed exome sequencing and array-based genotype analyses of 1477 Ashkenazi Jewish individuals with CD and 2614 Ashkenazi Jewish individuals without CD (controls). To validate our findings, we performed genotype analyses of an additional 1515 CD cases and 7052 controls for frameshift mutations in the colony-stimulating factor 2-receptor β common subunit gene (CSF2RB). Intestinal tissues and blood samples were collected from patients with CD; lamina propria leukocytes were isolated and expression of CSF2RB and granulocyte-macrophage colony-stimulating factor-responsive cells were defined by adenomatous polyposis coli (APC) time-of-flight mass cytometry (CyTOF analysis). Variants of CSF2RB were transfected into HEK293 cells and the expression and functions of gene products were compared. In the discovery cohort, weassociated CD with a frameshift mutation in CSF2RB (P=8.52× 10(-4)); the finding was validated in the replication cohort (combined P= 3.42× 10(-6)). Incubation of intestinal lamina propria leukocytes with granulocyte-macrophage colony-stimulating factor resulted in high levels of phosphorylation of signal transducer and activator of transcription (STAT5) and lesser increases in phosphorylation of extracellular signal-regulated kinase and AK straining transforming (AKT). Cells co-transfected withfull-length and mutant forms of CSF2RB had reduced pSTAT5 after stimulation with granulocyte-macrophage colony-stimulating factor, compared with cells transfected with control CSF2RB, indicating a dominant-negative effect of the mutant gene. Monocytes from patients with CD who were heterozygous for the frameshift mutation (6% of CD cases analyzed) hadreduced responses to granulocyte-macrophage colony-stimulating factor and markedly decreased activity of aldehyde dehydrogenase; activity of this enzyme has been associated with immune tolerance. In a genetic analysis of Ashkenazi Jewish individuals, we associated CD with a frameshift mutation in CSF2RB. Intestinal monocytes from carriers of this mutation had reduced responses to granulocyte-macrophage colony-stimulating factor, providing an additional mechanism for alterations to the innate immune response in individuals with CD.

Vegetal extracts influence in vitro on the cell-mediated immunity in carnivores depending on health status, target species and plant taxonomy

Impaired immune response in individuals subjected to various stress factors leads to disease or low protective responses following vaccination, therefore modern immunology is seeking for alternative immune stimulating compounds for which plants could represent a source. The aim of this study was to establish the influence of several ethanolic vegetal extracts on in vitro adaptive cell-mediated reactivity in wild (mink, n=70, silver foxes, n=22) and domestic (dogs, n=32) carnivores and compare the responsiveness of these species under physiological (antigen-primed) and pathophysiological (aleutian disase of mink) conditions. Mink and foxes were primed with a 5% SRBC suspension (0.5 and 1ml respectively), twice, 14days apart and blood was sampled on days 0 and 14, while untreated dogs were sampled only once. Ethanolic extracts of Calendula officinalis, Symphytum officinale, Arnica montana, Echinaceea angustifolia and Echinacea purpurea were tested for immune activity in whole blood cultures by the use of the in vitro blast transformation test, where cell growth was monitored spectrophotometrically, by the glucose consumption test and stimulation/inhibition indices (S/I) were calculated.E. angustifolia acted stimulating in Aleutian disease positive mink (S/I SRBC primed 76.75±12.52%, non-primed 19.58±18.07, p<0.001) and foxes (S/I primed 20.28±21.27%, non-primed 20.13±13.10), while S. officinale was most stimulating (3.85±1.37%) in dogs in a statistically supported manner (p<0.05).In conclusion, the results indicated the need of individualized immune stimulating therapies, based on species and health status in the studied species, with the prior identification of the most appropriate plant alcoholic extract for each species.

Crohn's Disease: Evolution, Epigenetics, and the Emerging Role of Microbiome-Targeted Therapies.

Crohn's disease (CD) is a chronic, systemic, immune-mediated inflammation of the gastrointestinal tract. Originally described in 1932 as non-caseating granulomatous inflammation limited to the terminal ileum, it is now recognized as an expanding group of heterogeneous diseases defined by intestinal location, extent, behavior, and systemic extraintestinal manifestations. Joint diseases, including inflammatory spondyloarthritis and ankylosing spondylitis, are the most common extraintestinal manifestations of CD and share more genetic susceptibility loci than any other inflammatory bowel disease (IBD) trait. The high frequency and overlap with genes associated with infectious diseases, specifically Mendelian susceptibility to mycobacterial diseases (MSMD), suggest that CD may represent an evolutionary adaptation to environmental microbes. Elucidating the diversity of the enteric microbiota and the protean mucosal immune responses in individuals may personalize microbiome-targeted therapies and molecular classifications of CD. This review will focus on CD's natural history and therapies in the context of epigenetics, immunogenetics, and the microbiome.

Characterization of clinical and immunological features in patients coinfected with dengue virus and HIV

The pathogenesis of dengue in subjects coinfected with HIV remains largely unknown. We investigate clinical and immunological parameters in coinfected DENV/HIV patients. According to the new dengue classification, most coinfected DENV/HIV patients presented mild clinical manifestations of dengue infection. Herein, we show that DENV/HIV coinfected patients had higher CD8 T cells percentages reflected as a lower CD4/CD8 ratio. Furthermore, CCR5 expression on CD4 T cells and CD107a expression on both T subsets were significantly higher in coinfected patients when compared with monoinfected DENV and HIV individuals respectively. Increased inflammatory response was observed in treated HAART coinfected patients despite undetectable HIV load. These data indicate that DENV infection may influence the clinical profile and immune response in individuals concomitantly infected with HIV.