The structure and dynamics of F-actin networks in the cortical area of B cells control the signal efficiency of B-cell antigen receptors (BCRs). Although antigen-induced signaling has been studied extensively, the role of cortical F-actin in antigen-independent tonic BCR signaling is less well understood. Because these signals are essential for the survival of B cells and are consequently exploited by several B-cell lymphomas, we assessed how the cortical F-actin structure influences tonic BCR signal transduction.
View Article and Find Full Text PDFB cell antigen receptor (BCR) signaling induces actin cytoskeleton remodeling by stimulating actin severing, actin polymerization, and the nucleation of branched actin networks via the Arp2/3 complex. This enables B cells to spread on antigen-bearing surfaces in order to increase antigen encounters and to form an immune synapse (IS) when interacting with antigen-presenting cells (APCs). Although the WASp, N-WASp, and WAVE nucleation-promoting factors activate the Arp2/3 complex, the role of WAVE2 in B cells has not been directly assessed.
View Article and Find Full Text PDFTIGIT is an inhibitory receptor expressed on lymphocytes and can inhibit T cells by preventing CD226 co-stimulation through interactions in cis or through competition of shared ligands. Whether TIGIT directly delivers cell-intrinsic inhibitory signals in T cells remains unclear. Here we show, by analysing lymphocytes from matched human tumour and peripheral blood samples, that TIGIT and CD226 co-expression is rare on tumour-infiltrating lymphocytes.
View Article and Find Full Text PDFOn March 30, 2020, the Government of Nigeria implemented its first COVID-19 related lockdown. We worked with two humanitarian projects in Nigeria, the Integrated Humanitarian Assistance to Northeast Nigeria (IHANN II) in Borno State and the United Nations High Commissioner for Refugees South-South Health and Nutrition Intervention (UNHCR-SS-HNIR) for Cameroon Refugees and vulnerable populations in Cross River State, to document the programmatic adaptations to Family Planning/Reproductive Health (FP/RH) services in response to COVID-19 and identify successes and challenges of those adaptations. A mixed methods approach including quantitative analysis of data from routine programmatic activities, qualitative data from in-depth interviews (IDIs) with project staff and process documentation of programmatic activities and modifications was used to 1) identify modifications in FP/RH services due to COVID-19, 2) understand staff perception of their utility and impact, and 3) gauge trends in key FP/RH in-service delivery indicators to assess changes prior to and after the March 2020 lockdown.
View Article and Find Full Text PDFHere, we describe a method, which we term "shadow imaging," to analyze the secretions of individual cells at immune synapses or other cell contacts. Following immune synapse formation and cellular activation on ligand-rich slides, the position of each cell is recorded using a pulsed immunofluorescence stain against the proteins on the ligand-rich slide surface. The pulsed stain does not penetrate the synaptic cleft, resulting in an unlabeled region or "shadow" beneath cells that is retained following cellular detachment.
View Article and Find Full Text PDFRev Panam Salud Publica
November 2022
The life course approach effectively responds to pressing health needs and fills critical gaps to improve health outcomes in the era of COVID-19 and beyond. This article outlines four main reasons to adopt and implement the life course approach in public health at national and local levels: (i) the approach effectively responds to new health trends and evidence, (ii) it fills longstanding gaps in care, (iii) it best addresses health inequities, and (iv) it can help achieve more with less.
View Article and Find Full Text PDFBackground: Community Heart Health Actions for Latinos at Risk (CHARLAR) is a promotora-led cardiovascular disease (CVD) risk-reduction program for socio-demographically disadvantaged Latinos and consists of 11 skill-building sessions. The COVID-19 pandemic has led to worsening health status in U.S.
View Article and Find Full Text PDFThe diverse origins, nanometre-scale and invasive isolation procedures associated with extracellular vesicles (EVs) mean they are usually studied in bulk and disconnected from their parental cell. Here, we used super-resolution microscopy to directly compare EVs secreted by individual human monocyte-derived macrophages (MDMs). MDMs were differentiated to be M0-, M1- or M2-like, with all three secreting EVs at similar densities following activation.
View Article and Find Full Text PDFCytotoxic lymphocytes are critical in our immune defence against cancer and infection. Cytotoxic T lymphocytes and Natural Killer cells can directly lyse malignant or infected cells in at least two ways: granule-mediated cytotoxicity, involving perforin and granzyme B, or death receptor-mediated cytotoxicity, involving the death receptor ligands, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL). In either case, a multi-step pathway is triggered to facilitate lysis, relying on active pro-death processes and signalling within the target cell.
View Article and Find Full Text PDFExtracellular vesicles (EVs) released from activated platelets contain microRNAs, the most abundant of which is hsa-miR-223-3p. Endogenous hsa-miR-223-3p suppresses the expression of tissue factor (TF), the initiator of the extrinsic coagulation pathway, in endothelial cells. Monocytes can be induced to express TF to enhance coagulation, but the role of hsa-miR-223-3p in regulating monocyte TF remains unknown.
View Article and Find Full Text PDFThe impact of radiotherapy on the interaction between immune cells and cancer cells is important not least because radiotherapy can be used alongside immunotherapy as a cancer treatment. Unexpectedly, we found that X-ray irradiation of cancer cells induced significant resistance to natural killer (NK) cell killing. This was true across a wide variety of cancer-cell types as well as for antibody-dependent cellular cytotoxicity.
View Article and Find Full Text PDFInterleukin 1β (IL-1β) plays a major role in inflammation and is secreted by immune cells, such as macrophages, upon recognition of danger signals. Its secretion is regulated by the inflammasome, the assembly of which results in caspase 1 activation leading to gasdermin D (GSDMD) pore formation and IL-1β release. During inflammation, danger signals also activate the complement cascade, resulting in the formation of the membrane attack complex (MAC).
View Article and Find Full Text PDFOne mechanism by which monoclonal antibodies (mAb) help treat cancer or autoimmune disease is through triggering antibody-dependent cellular cytotoxicity (ADCC) CD16 on Natural Killer (NK) cells. Afucosylation is known to increase the affinity of mAbs for CD16 on NK cells and here, we set out to assess how mAb afucosylation affects the dynamics of NK cell interactions, receptor expression and effector functions. An IgG1 version of a clinically important anti-CD20 mAb was compared to its afucosylated counterpart (anti-CD20-AF).
View Article and Find Full Text PDFObserving the cell surface and underlying cytoskeleton at nanoscale resolution using super-resolution microscopy has enabled many insights into cell signaling and function. However, the nanoscale dynamics of tissue-specific immune cells have been relatively little studied. Tissue macrophages, for example, are highly autofluorescent, severely limiting the utility of light microscopy.
View Article and Find Full Text PDFObjectives: This paper evaluates the cost-effectiveness of rebranding former traditional birth attendants (TBAs) to conduct health promotion activities and refer women to health facilities.
Methods: The project used 200 former TBAs, 100 of whom were also enrolled in a small income generating business. The evaluation had a three-arm, quasiexperimental design with baseline and endline household surveys.
Natural killer (NK) cells form immune synapses to ascertain the state of health of cells they encounter. If a target cell triggers NK cell cytotoxicity, lytic granules containing proteins including perforin and granzyme B, are secreted into the synaptic cleft inducing target cell death. Secretion of these proteins also occurs from activated cytotoxic T lymphocytes (CTLs) where they have recently been reported to complex with thrombospondin-1 (TSP-1) in specialized structures termed supramolecular attack particles (SMAPs).
View Article and Find Full Text PDFNatural Killer (NK) cells can engage multiple virally infected or tumor cells sequentially and deliver perforin for cytolytic killing of these targets. Using microscopy to visualize degranulation from individual NK cells, we found that repeated activation via the Fc receptor CD16 decreased the amount of perforin secreted. However, perforin secretion was restored upon subsequent activation via a different activating receptor, NKG2D.
View Article and Find Full Text PDFOn activation platelets release microRNAs and extracellular vesicles (EV) into circulation. The release of EV from platelets has been shown to be dependent on the agonist; in this study, we investigated whether the microRNA profile or EV released from platelets was also agonist specific. Washed platelets from healthy subjects were maximally stimulated with agonists specific for the receptors for collagen (Glycoprotein VI (GPVI)), thrombin (PAR1/PAR4), or ADP (P2Y1/P2Y12) with/without inhibiting secondary mediators, using aspirin to block cyclooxygenase-1 and apyrase to remove ADP.
View Article and Find Full Text PDFThe complex interplay between cancer cells, stromal cells, and immune cells in the tumor microenvironment (TME) regulates tumorigenesis and provides emerging targets for immunotherapies. Crosstalk between CD4(+) T cells and proliferating chronic lymphocytic leukemia (CLL) tumor B cells occurs within lymphoid tissue pseudofollicles, and investigating these interactions is essential to understand both disease pathogenesis and the effects of immunotherapy. Tumor-derived extracellular vesicle (EV) shedding is emerging as an important mode of intercellular communication in the TME.
View Article and Find Full Text PDFRev Panam Salud Publica
December 2014
This report describes 1) the evaluation of the Familias Fuertes primary prevention program in three countries (Bolivia, Colombia, and Ecuador) and 2) the effect of program participation on parenting practices. Familias Fuertes was implemented in Bolivia (10 groups, 96 parents), Colombia (12 groups, 173 parents), and Ecuador (five groups, 42 parents) to prevent the initiation and reduce the prevalence of health-compromising behaviors among adolescents by strengthening family relationships and enhancing parenting skills. The program consists of seven group sessions (for 6-12 families) designed for parents/caregivers and their 10-14-year-old child.
View Article and Find Full Text PDFThe physiological properties of vertebrate skeletal muscle typically show a scaling pattern of slower contractile properties with size. In fishes, the myotomal or swimming muscle reportedly follows this pattern, showing slower muscle activation, relaxation and maximum shortening velocity (V(max)) with an increase in body size. We asked if the muscles involved in suction feeding by fishes would follow the same pattern.
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