Lung dendritic cells are primed by inhaled particulate antigens, and retain MHC class II/antigenic peptide complexes in hilar lymph nodes for a prolonged period of time

Intratracheal (IT) administration of heat-killed Listeria monocytogenes (HKL) results in an influx of macrophage and dendritic cell (DC) precursors into the lung interstitium. Low-density, FcR+, interstitial lung cells isolated from rats instilled 24 hr before with HKL or vehicle alone, were > 90% Mar1+. After culturing with granulocyte-macrophage colony-stimulating factor (GM-CSF) for 3 days, up to 24% of the loosely adherent cells were DC that stimulated allogeneic T-cell proliferation in an mixed lymphocyte reaction (MLR) assay. After only an overnight incubation with GM-CSF, however, the capacity of interstitial Mar1+ cells to stimulate HKL immune T-cell proliferation without exogenous antigen was low. By contrast, when DC were isolated as major histocompatibility complex (MHC) class II+ cells from rat lungs at 1, 3, 7 and 14 days after HKL instillation and cultured overnight with GM-CSF, their antigen presentation capacity without added exogenous antigen was robust, but declined over the 2-week period. Interestingly, hilar lymph node DC maintained their HKL antigen-presenting capacity for up to 2 weeks after instillation of HKL. Following IT administration of PKH-26 labelled HKL, fluorescent or immunolabelled organisms were detected in OX62+ DC in airway epithelium, lung interstitium and hilar lymph nodes in situ and in MHC class II+ DC isolated from these sites. We conclude that newly immigrated Mar1+ lung DC precursors, while efficient in endocytosing particulate antigens, are incapable of eliciting a significant proliferative response from HKL-sensitized T cells. By contrast, MHC class II+ DC isolated from lungs and incubated overnight with GM-CSF induce vigorous antigen-specific T-cell proliferation. Antigen-loaded lung DC in hilar lymph nodes maintain their antigen presentation capacity for up to 2 weeks.     

Quantitative differences in lipid raft components between murine CD4<Superscript>+</Superscript> and CD8<Superscript>+</Superscript> T cells

Background  

Lipid rafts have been shown to play a role in T cell maturation, activation as well as in the formation of immunological synapses in CD4⁺ helper and CD8⁺ cytotoxic T cells. However, the differential expression of lipid raft components between CD4⁺ and CD8⁺ T cells is still poorly defined. To examine this question, we analyzed the expression of GM1 in T cells from young and aged mice as well as the expression of the glycosylphosphatidylinositol (GPI)-linked protein Thy-1 and cholesterol in murine CD4⁺ and CD8⁺ T cell subpopulations.     

Loss of imprinting of IGF2 and H19 in osteosarcoma is accompanied by reciprocal methylation changes of a CTCF-binding site

The adjacent insulin-like growth factor 2 (IGF2) and H19 genes are imprinted in most normal human tissues, but imprinting is often lost in tumors. The mechanisms involved in maintenance of imprinting (MOI) and loss of imprinting (LOI) are unresolved. We show here that osteosarcoma (OS) tumors with IGF2/H19 MOI exhibit allele-specific differential methylation of a CTCF-binding site upstream of H19. LOI of IGF2 or H19 in OS occurs in a mutually exclusive manner, and occurs with monoallelic expression of the other gene. Bisulfite sequencing reveals IGF2 LOI occurs with biallelic CpG methylation of the CTCF-binding site, while H19 LOI occurs with biallelic hypomethylation of this site. Our data demonstrate that IGF2 LOI and H19 LOI are accompanied by reciprocal methylation changes at a critical CTCF-binding site. We propose a model in which incomplete gain or loss of methylation at this CTCF-binding site during tumorigenesis explains the complex and often conflicting expression patterns of IGF2 and H19 in tumors.     

Humoral immunity to immunodominant epitopes of Hepatitis C virus in individuals infected with genotypes 1a or 1b

Cellular immunity against multiple Hepatitis C virus (HCV) proteins is observed in patients acutely infected with HCV most of whom later resolve infection. We wished to assess humoral immunity in patients infected with HCV 1a or 1b genotypes in relation to viral load using plasma samples from HCV-infected individuals and a panel of peptides representing immunodominant epitopes of HCV structural and nonstructural proteins. Plasma from HCV 1a- and 1b-infected patients, respectively, were divided into two groups: patients with low viral load (<==100,000 RNA copies/ml) and patients with high viral load (>/=10,000,000 RNA copies/ml). The antigens were peptides representing epitopes from immunodominant regions of HCV core, E2, NS3, and NS4 proteins, as well as the hypervariable (HVR) epitopes in E2 from genotypes 1a and 1b. Individuals infected with HCV 1a evoked a stronger immune response to many immunodominant epitopes of HCV relative to individuals infected with HCV 1b. Moreover, among individuals infected with HCV 1a, those with low viral loads mounted significantly greater responses against these epitopes than did individuals with high viral loads. Our observations demonstrate that quantitatively different antibody responses are elicited against HCV depending on the genotype of infecting virus, and suggest that humoral immunity directed against multiple immunodominant epitopes in HCV 1a-infected individuals may help lower viral load in vivo.     

Detection and characterization of diarrheagenic Escherichia coli from young children in Hanoi, Vietnam

Diarrhea continues to be one of the most common causes of morbidity and mortality among infants and children in developing countries. Escherichia coli is an emerging agent among pathogens that cause diarrhea. The development of a highly applicable technique for the detection of different categories of diarrheagenic E. coli is important. We have used multiplex PCR by combining eight primer pairs specific for enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), enterohemorrhagic E. coli, enteropathogenic E. coli (EPEC), and enterotoxigenic E. coli (ETEC). This facilitates the identification of five different categories of diarrheagenic E. coli from stool samples in a single reaction simultaneously. The prevalences of diarrheagenic E. coli were 22.5 and 12% in the diarrhea group and the control group, respectively. Among 587 fecal samples from Vietnamese children under 5 years of age with diarrhea, this technique identified 132 diarrheagenic E. coli strains. This included 68 samples (11.6%) with EAEC, 12 samples (2.0%) with EIEC, 39 samples (6.6%) with EPEC, and 13 samples (2.2%) with ETEC. Among the 249 age-matched controls, 30 samples were positive for diarrheagenic E. coli. The distribution was 18 samples (7.2%) with EAEC, 11 samples (4.4%) with EPEC, and 1 sample (0.4%) with ETEC.     

Key Informants’ Perspectives on Childhood Obesity in Vietnam: A Qualitative Study

Maternal and Child Health Journal - Vietnam’s post-war globalization, economic development, and urbanization have contributed to a nutrition transition from traditional diets to...     

Dietary Behaviors and Incident COVID-19 in the UK Biobank

Background: Nutritional status influences immunity but its specific association with susceptibility to COVID-19 remains unclear. We examined the association of specific dietary data and incident COVID-19 in the UK Biobank (UKB). Methods: We considered UKB participants in England with self-reported baseline (2006–2010) data and linked them to Public Health England COVID-19 test results—performed on samples from combined nose/throat swabs, using real time polymerase chain reaction (RT-PCR)—between March and November 2020. Baseline diet factors included breastfed as baby and specific consumption of coffee, tea, oily fish, processed meat, red meat, fruit, and vegetables. Individual COVID-19 exposure was estimated using the UK’s average monthly positive case rate per specific geo-populations. Logistic regression estimated the odds of COVID-19 positivity by diet status adjusting for baseline socio-demographic factors, medical history, and other lifestyle factors. Another model was further adjusted for COVID-19 exposure. Results: Eligible UKB participants (n = 37,988) were 40 to 70 years of age at baseline; 17% tested positive for COVID-19 by SAR-CoV-2 PCR. After multivariable adjustment, the odds (95% CI) of COVID-19 positivity was 0.90 (0.83, 0.96) when consuming 2–3 cups of coffee/day (vs. <1 cup/day), 0.88 (0.80, 0.98) when consuming vegetables in the third quartile of servings/day (vs. lowest quartile), 1.14 (1.01, 1.29) when consuming fourth quartile servings of processed meats (vs. lowest quartile), and 0.91 (0.85, 0.98) when having been breastfed (vs. not breastfed). Associations were attenuated when further adjusted for COVID-19 exposure, but patterns of associations remained. Conclusions: In the UK Biobank, consumption of coffee, vegetables, and being breastfed as a baby were favorably associated with incident COVID-19; intake of processed meat was adversely associated. Although these findings warrant independent confirmation, adherence to certain dietary behaviors may be an additional tool to existing COVID-19 protection guidelines to limit the spread of this virus.