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Well‐being is increasingly being promoted and used to describe social progress. However, tension exists between framings that focus on enhancing individual well‐being (living well) and societal or collective framings of well‐being (living well together). Well‐being is central to Aotearoa New Zealand's COVID‐19 response and recovery. The COVID‐19 pandemic reopened debates about what kind of society people want to live in. Our research explored the 'shared typical' or commonality of experiences of the first wave of COVID‐19 response in Aotearoa New Zealand. Semi‐structured interviews provided insights into a wide range of concerns participants faced and what that meant for their well‐being and the well‐being of Aotearoa New Zealand. We found that well‐being is both multidimensional and hierarchical, and while people talked about their own well‐being, it was often in the context of broader social well‐being. These findings support research showing that well‐being is relational. We suggest that Indigenous models of well‐being are well placed to inform policy strategies enabling holistic well‐being, but this needs to be done in ways that pair Indigenous and Western knowledge, rather than integrating or assimilating this knowledge into Western science approaches. [ABSTRACT FROM AUTHOR]

Introduction: Structural stigma in the global HIV response is a "moving target" that constantly evolves as the epidemic changes. Tackling structural stigma requires an understanding of the drivers and facilitators of stigma in complex community, policy and health systems. In this paper, we present findings from a study adopting a systems perspective to understand how to tackle structural stigma via the Meaningful Involvement of People with HIV/AIDS (MIPA), while highlighting the challenges in demonstrating peer leadership from people living with HIV (PLHIV). Methods: Through a long‐term ongoing community‐research collaboration (2015–2023), the study applied systems thinking methods to draw together the insights of over 90 peer staff from 10 Australian community and peer organizations. We used hypothetical narratives, affinity methods and causal loop diagrams to co‐create system maps that visualize the factors that influence the extent to which peer leadership is expected, respected, sought‐out and funded in the Australian context. We then developed draft indicators of what we should see happening when PLHIV peer leadership and MIPA is enabled to challenge structural stigma. Results: Participants in the collaboration identified the interactions at a system level, which can enable or constrain the quality and influence of PLHIV peer leadership. Participants identified that effective peer leadership is itself affected by structural stigma, and peer leaders and the programmes that support and enable peer leadership must navigate a complex network of causal pathways and strategic pitfalls. Participants identified that indicators for effective PLHIV peer leadership in terms of engagement, alignment, adaptation and influence also required indicators for policy and service organizations to recognize their own system role to value and enable PLHIV peer leadership. Failing to strengthen and incorporate PLHIV leadership within broader systems of policy making and health service provision was identified as an example of structural stigma. Conclusions: Incorporating PLHIV leadership creates a virtuous cycle, because, as PLHIV voices are heard and trusted, the case for their inclusion only gets stronger. This paper argues that a systems perspective can help to guide the most productive leverage points for intervention to tackle structural stigma and promote effective PLHIV leadership. [ABSTRACT FROM AUTHOR]

Carboxypeptidase, vitellogenic-like (CPVL) is a serine carboxypeptidase of unknown function that was first characterized in human macrophages. Initial studies suggested that CPVL is largely restricted to the monocytic lineage, although it may also be expressed by cells outside the immune system. Here, we use a new monoclonal antibody to characterize the properties and localization of CPVL in human macrophages to elucidate a possible function for the protease. CPVL is up-regulated during the maturation of monocytes (MO) to macrophages, although the protein can be seen in both. In primary macrophages, CPVL is glycosylated with high mannose residues and colocalizes with markers for endoplasmic reticulum, while in MO it is more disperse and less clearly associated with endoplasmic reticulum. CPVL is highly expressed in lamellipodia and membrane ruffles, which also concentrate markers of the secretory pathway (MIP-1α and tumour necrosis factor-α) and major histocompatibility complex (MHC) class I and II molecules. CPVL can be seen on early latex bead and Candida albicans phagosomes, but it is not retained in the maturing phagosome, unlike MHC class I/II. CPVL has a mixed cytosolic and membrane-associated localization but is not detectable on the outer plasma membrane. We propose that CPVL may be involved in antigen processing, the secretory pathway and/or in actin remodelling and lamellipodium formation. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLR) have been described as partially sharing signalling pathways but showing unique ligand specificity and tissue distribution. Here, the response of bovine macrophages (Mφ) and dendritic cells (DC), both derived from monocytes, was compared by exposing them to the TLR-specific ligands lipopolysaccharide, poly(I:C)-double-stranded RNA, and CpG-DNA, as well as inactivated Gram-negative and Gram-positive bacteria, shown to bind to TLR. The production of NO, superoxide anion, interleukin-10 (IL-10), IL-12 and tumour necrosis factor (TNF) was determined. Compared to monocytes, Mφ expressed more TLR2 and similar levels of TLR4 mRNA transcripts, as analysed by quantitative polymerase chain reaction, whereas DC expressed reduced amounts. Although both DC and Mφ recognized the TLR ligands, dramatic differences were seen in their reaction pattern to them. Both cell types responded with the production of TNF, but DC produced more IL-12, whereas Mφ produced more IL-10, regardless of the TLR agonist used. Co-stimulation with interferon-γ influenced the amount of cytokine production, but did not alter the cell type-specific response pattern. Compared to Mφ, DC produced > 10 times less NO upon triggering with TLR ligands. In addition, DC produced superoxide anion to opsonized and non-opsonized zymosan, but not to phorbol 12-myristate 13-acetate, a response pattern confirmed for human Mφ and DC, respectively. Different protein kinase C isoforms and extracellular signal-regulated kinase patterns were detected in cell lysates of resting and stimulated Mφ and DC. Collectively, our results point to profound differences in pathogen-derived signal–response coupling occurring commensurate with distinct functions carried out by Mφ or DC. [ABSTRACT FROM AUTHOR]

Summary Two phenotypically distinct subpopulations of dendritic cells (SIRPα[sup +] CC81Ag[sup -] DC and SIRPα[sup -] CC81Ag[sup +] DC) have previously been identified in bovine afferent lymph which show functional differences when assayed in vitro . The purpose of this study was to investigate whether differences in cytokine production between the two subpopulations might occur which could influence the bias of the immune response they stimulate. Qualitative and quantitative polymerase chain reactions were used to detect specific mRNA transcripts and flow cytometry and enzyme-linked immunosorbent assays were used to detect protein production. The SIRPα[sup -] CC81Ag[sup +] DC produced considerably more interleukin-12 (IL-12) mRNA transcripts and protein than the SIRPα[sup +] CC81Ag[sup -] DC. Conversely, SIRPα[sup +] CC81Ag[sup -] DC contained more of both transcripts and protein for IL-1 and of transcripts for IL-6. A small percentage of both subpopulations produced interferon-γ (IFN-γ) as evidenced by cytoplasmic staining. Stimulation of DC by culture with CD40L[sup +] cells increased the production of IL-1, IL-6 and IL-12 but quantitative differences between the subpopulations remained. Production of IL-10 was also evident following culture with CD40L[sup +] cells or lipopolysaccharide primarily by the SIRPα[sup +] CC81Ag[sup -] DC. No evidence was found for type 1 IFN production, and hence plasmacytoid DC, by DC in afferent lymph; both subpopulations appear to be myeloid in origin. These different cytokine repertoires of the two subpopulations of ex vivo DC isolated from afferent lymph imply functional differences that could influence the presentation of antigen to T cells and bias of the immune response following vaccination or infection. [ABSTRACT FROM AUTHOR]

Summary Caveolin is a generic term for a family of proteins that include caveolin-1, -2 and -3. Although the distribution of these proteins varies between cells, caveolin-1 and -2 are commonly found coating membrane invaginations known as caveolae. Studies on human and murine cells suggest that caveolin/caveolae can be found in neutrophils, macrophages and mast cells, in which they are involved in the uptake of pathogens, but not in lymphocyte cell lines. Expression of caveolin-1, -2 and -3 in bovine immune cells was investigated using confocal microscopy and Western blotting. Staining for caveolin-1 was evident in all peripheral blood mononuclear cells (PBMC) and in CD4+, CD8+ and CD21+ lymphocytes, monocytes, macrophages and monocyte-derived dendritic cells (DC). In addition, the caveolin-1 antibody detected a protein with a molecular weight of approximately 22 000 in all PBMC, macrophages and DC, as well as in bovine aortic endothelial (BAE)-1 cells and human endothelial cells by Western blotting. In macrophages and DC, caveolin co-localized with the endoplasmic reticulum–Golgi intermediate compartment (ERGIC) and to a lesser extent with Golgi, but not with endoplasmic reticulum. Staining was not seen on the plasma membrane in any bovine immune cells, suggesting the absence of caveolae, while in BAE-1 cells staining was predominantly on the cell membrane. Caveolin-2 could not be detected in any bovine cells by confocal microscopy or Western blotting, while caveolin-3 was detected in all bovine cells by Western blotting, but not by confocal microscopy. These data provide evidence for the presence of caveolin in bovine lymphocytes and antigen-presenting cells. [ABSTRACT FROM AUTHOR]