Serum-Mediated Activation of Macrophages Reflects TcVac2 Vaccine Efficacy against Chagas Disease

Chagas disease is endemic in Latin America and an emerging infectious disease in the United States. No effective treatments are available. The TcG1, TcG2, and TcG4 antigens are highly conserved in clinically relevant Trypanosoma cruzi isolates and are recognized by B and T cells in infected hosts. Delivery of these antigens as a DNA prime/protein boost vaccine (TcVac2) elicited lytic antibodies and type 1 CD8⁺ T cells that expanded upon challenge infection and provided >90% control of parasite burden and myocarditis in chagasic mice. Here we determined if peripheral blood can be utilized to capture the TcVac2-induced protection from Chagas disease. We evaluated the serum levels of T. cruzi kinetoplast DNA (TckDNA), T. cruzi 18S ribosomal DNA (Tc18SrDNA), and murine mitochondrial DNA (mtDNA) as indicators of parasite persistence and tissue damage and monitored the effect of sera on macrophage phenotype. Circulating TckDNA/Tc18SrDNA and mtDNA were decreased by >3- to 5-fold and 2-fold, respectively, in vaccinated infected mice compared to nonvaccinated infected mice. Macrophages incubated with sera from vaccinated infected mice exhibited M2 surface markers (CD16, CD32, CD200, and CD206), moderate proliferation, a low oxidative/nitrosative burst, and a regulatory/anti-inflammatory cytokine response (interleukin-4 [IL-4] plus IL-10 > tumor necrosis factor alpha [TNF-α]). In comparison, macrophages incubated with sera from nonvaccinated infected mice exhibited M1 surface markers, vigorous proliferation, a substantial oxidative/nitrosative burst, and a proinflammatory cytokine response (TNF-α ≫ IL-4 plus IL-10). Cardiac infiltration of macrophages and TNF-α and oxidant levels were significantly reduced in TcVac2-immunized chagasic mice. We conclude that circulating TcDNA and mtDNA levels and macrophage phenotype mediated by serum constituents reflect in vivo levels of parasite persistence, tissue damage, and inflammatory/anti-inflammatory state and have potential utility in evaluating disease severity and efficacy of vaccines and drug therapies.     

Interleukin‐22 Reduces the Severity of Collagen‐Induced Arthritis in Association With Increased Levels of Interleukin‐10

Objective

The mechanism of action of interleukin‐ 22 (IL‐22) in inflammatory arthritis remains unknown. IL‐22–deficient mice exhibit an intact humoral and cellular immune response to collagen and yet have a reduced incidence of collagen‐induced arthritis (CIA). Further, administration of anti–IL‐22 does not reduce the severity of clinical arthritis but rather improves only certain aspects of joint inflammation as assessed histologically. This study was undertaken to investigate the mechanism of action and role of systemic IL‐22 in modulating target organ inflammation.

Methods

CIA was induced in DBA mice by immunization with collagen and Freund's complete adjuvant. Expression of IL‐22 and its receptor (IL‐22R) in lymphoid organ and target tissues was determined during various phases of arthritis. The effector functions of IL‐22 on induction/regulation of various cytokines in in vitro restimulation cultures were analyzed by enzyme‐linked immunosorbent assay (ELISA). Recombinant IL‐22 with or without anti–IL‐10 antibody was administered to mice following immunization with collagen and prior to the onset of arthritis, and the severity of arthritis was evaluated by clinical scoring and histopathologic assessment. Anticollagen antibodies in mouse sera were analyzed by ELISA.

Results

IL‐22 and IL‐22R were up‐regulated in lymphoid organs and joints during the course of arthritis. IL‐22 augmented IL‐10, IL‐17, and IL‐6 in lymphoid tissues in vitro. Administration of recombinant IL‐22 was associated with an increase in IL‐10 levels in vivo and a significant reduction in the progression of arthritis severity. Anti–IL‐10 antibody treatment was associated with the abrogation of this protective effect of IL‐22.

Conclusion

Our data demonstrate, for the first time, that IL‐22 has a protective role in inflammatory arthritis.

     

Knowledge of stroke among stroke patients and their relatives in Northwest India

BACKGROUND: The knowledge of warning symptoms and risk factors for stroke has not been studied among patients with stroke in developing countries. AIMS: We aimed to assess the knowledge of stroke among patients with stroke and their relatives. SETTINGS AND DESIGN: Prospective tertiary referral hospital-based study in Northwest India. MATERIALS AND METHODS: Trained nurses and medical interns interviewed patients with stroke and transient ischemic attack and their relatives about their knowledge of stroke symptoms and risk factors. STATISTICAL ANALYSIS: Univariable and multivariable logistic regression were used. RESULTS: Of the 147 subjects interviewed, 102 (69%) were patients and 45 (31%) were relatives. There were 99 (67%) men and 48 (33%) women and the mean age was 59.7+/-14.1 years. Sixty-two percent of respondents recognized paralysis of one side as a warning symptom and 54% recognized hypertension as a risk factor for stroke. In the multivariable logistic regression analysis, higher education was associated with the knowledge of correct organ involvement in stroke (OR 2.6, CI 1.1- 6.1, P =0.02), whereas younger age (OR 2.7, CI 1.1-7.0, P =0.04) and higher education (OR 4.1, CI 1.5-10.9, P =0.005) correlated with a better knowledge regarding warning symptoms of stroke. CONCLUSIONS: In this study cohort, in general, there is lack of awareness of major warning symptoms, risk factors, organ involvement and self-recognition of stroke. However younger age and education status were associated with better knowledge. There is an urgent need for awareness programs about stroke in this study cohort.     

Adhesion molecule expression and ventricular remodeling in chronic rheumatic heart disease: a cause or effect in the disease progression--a pilot study

BackgroundRheumatic fever and chronic rheumatic heart disease (RHD) remains one of the most important causes of cardiovascular morbidity leading to a major public health problem, especially in developing countries. This was a pilot study to assess the presence of inflammation and expression of adhesion molecules by immunohistochemistry (IHC) in endomyocardial biopsy specimens of patients with chronic RHD.MethodsEndomyocardial biopsy was obtained from 14 patients of chronic RHD with no features of activity clinically. Biopsies were processed for histology and IHC. IHC was carried using monoclonal antibodies against CD3, CD4, CD8, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1.ResultsHistomorphologically, varying degree of interstitial and perivascular fibrosis was seen in all the 13 patients (100%). Mild fibrosis (1+) was seen in five patients (38.5%); moderate interstitial fibrosis (2+) was present in four patients (30.8%).There was no Aschoff nodule or evidence of active myocarditis in any of the biopsy specimens.ImmunohistochemistryModerate positivity of (2+) and intense positivity of (3+) for intercellular adhesion molecule-1 was seen in 11 and 2 patients, respectively. With vascular cell adhesion molecule-1, four showed mild positivity (1+), and three showed intense positivity (3+). The phenotypic analysis of the inflammatory cells in our study revealed CD8⁺ cells in 77%, CD4⁺ in 23.1%, and CD3⁺ in 38.5% of total patients, which suggests chronicity.ConclusionThe nonspecific histomorphological changes and increased adhesion molecules expression could be a part of the ventricular remodeling due to the hemodynamic stress by the stenotic or regurgitant lesions of RHD itself.     

Disordered eating and eating disorders among women seeking fertility treatment: A systematic review

The purpose of this systematic review is to evaluate the prevalence of disordered eating and eating disorders among women seeking fertility treatment.

Observational studies were searched in Ovid MEDLINE, Web of Science, Embase, and PsycInfo. Studies published prior to September 2020 when the search was conducted were considered. Inclusion criteria included (1) original and empirical research, (2) published in a peer-reviewed journal, and (3) reported on disordered eating among women seeking fertility treatment in the sample or reported on prevalence of eating disorders among women seeking fertility treatment in the sample. Independent screening of abstracts was conducted by two authors (LH and AH). Ten studies met the inclusion criteria. Sample size, study location, measures, and results for each study in this review were reported.

Among women pursuing fertility treatment, rates of current eating disorders ranged from 0.5 to 16.7%, while past eating disorder prevalence rates ranged from 1.4 to 27.5%. Current anorexia nervosa or bulimia nervosa was reported by up to 2% and 10.3% of women, respectively, while history of anorexia nervosa or bulimia nervosa was reported by up to 8.5% and 3.3% of women, respectively. Binge eating disorder or other eating disorders were reported by up to 18.5% and 9.1% of women, respectively. Disordered eating pathology was endorsed by 1.6 to 48% of women seeking fertility treatment. Endorsement of pathological eating attitudes was generally higher among women seeking fertility treatment with current or past eating disorders as compared to community samples, with the exception of dietary restraint. Rates of current and past eating disorders are higher among women seeking fertility treatment than in the general population. Providers treating women with infertility should be cognizant of these prevalence rates and consider screening for eating pathology in their patients as this may contribute to their likelihood of successful conception and/or subsequent pregnancy outcomes.

     

Conserved MHC class I-presented dengue virus epitopes identified by immunoproteomics analysis are targets for cross-serotype reactive T-cell response

Dengue fever and dengue hemorrhagic fever are significant global public health problems, and understanding the overall immune response to infection will contribute to appropriate management of the disease and its potentially severe complications. Live attenuated and subunit vaccine candidates, which are under clinical evaluation, induce primarily an antibody response to the virus and minimal cross-reactive T-cell responses. Currently, there are no available tools to assess protective T-cell responses during infection or after vaccination. In this study, we utilize an immunoproteomics process to uncover novel HLA-A2-specific epitopes derived from dengue virus (DV)-infected cells. These epitopes are conserved, and we report that epitope-specific cytotoxic lymphocytes (CTLs) are cross-reactive against all 4 DV serotypes. These epitopes have potential as new informational and diagnostic tools to characterize T-cell immunity in DV infection and may serve as part of a universal vaccine candidate complementary to current vaccines in trial.