A software tool for estimation of burden of infectious diseases in Europe using incidence-based disability adjusted life years

The burden of disease framework facilitates the assessment of the health impact of diseases through the use of summary measures of population health such as Disability- Adjusted Life Years (DALYs). However, calculating, interpreting and communicating the results of studies using this methodology poses a challenge. The aim of the Burden of Commu

Blimp-1 Rather Than Hobit Drives the Formation of Tissue-Resident Memory CD8+ T Cells in the Lungs

Tissue-resident memory CD8+ T (TRM) cells that develop in the epithelia at portals of pathogen entry are important for improved protection against re-infection. CD8+ TRM cells within the skin and the small intestine are long-lived and maintained independently of circulating memory CD8+ T cells. In contrast to CD8+ TRM cells at these sites, CD8+ TRM cells that arise after influenza virus infection within the lungs display high turnover and require constant recruitment from the circulating memory pool for long-term persistence. The distinct characteristics of CD8+ TRM cell maintenance within the lungs may suggest a unique program of transcriptional regulation of influenza-specific CD8+ TRM cells. We have previously demonstrated that the transcription factors Hobit and Blimp-1 are essential for the formation of CD8+ TRM cells across several tissues, including skin, liver, kidneys, and the small intestine. Here, we addressed the roles of Hobit and Blimp-1 in CD8+ TRM cell differentiation in the lungs after influenza infection using mice deficient for these transcription factors. Hobit was not required for the formation of influenza-specific CD8+ TRM cells in the lungs. In contrast, Blimp-1 was essential for the differentiation of lung CD8+ TRM cells and inhibited the differentiation of central memory CD8+ T (TCM) cells. We conclude that Blimp-1 rather than Hobit mediates the formation of CD8+ TRM cells in the lungs, potentially through control of the lineage choice between TCM and TRM cells during the differentiation of influenza-specific CD8+ T cells

Impact of infectious diseases on population health using incidence-based disability-adjusted life years (DALYs)

Background and aims: The Burden of Communicable Diseases in Europe (BCoDE) study aimed to calculate disability-adjusted life years (DALYs) for 31 selected diseases in the European Union (EU) and European Economic Area (EEA). Methods: DALYs were estimated using an incidence-based and pathogen-based approach. Incidence was estimated through assessment of data availability and quality, and a correction was applied for under-estimation. Calculation of DALYs was performed with the BCoDE software toolkit without applying time discounting and age-weighting. Results: W

The contribution of macroalgae-associated fishes to small-scale tropical reef fisheries

Macroalgae-dominated reefs are a prominent habitat in tropical seascapes that support a diversity of fishes, including fishery target species. To what extent, then, do macroalgal habitats contribute to small-scale tropical reef fisheries? To address this question we: (1) Quantified the macroalgae-associated fish component in catches from 133 small-scale fisheries, (2) Compared life-history traits relevant to fishing (e.g. growth, longevity) in macroalgal and coral-associated fishes, (3) Examined how macroalgae-associated species can influence catch diversity, trophic level and vulnerability and (4) Explored how tropical fisheries change with the expansion of macroalgal habitats using a case study of fishery-independent data for Seychelles. Fish that utilised macroalgal habitats comprise 24% of the catch, but very few fished species relied entirely on macroalgal or coral habitats post-settlement. Macroalgal and coral-associated fishes had similar life-history traits, although vulnerability to fishing declined with increasing contribution of macroalgae association to the catch, whilst mean trophic level and diversity peaked when macroalgal-associated fish accounted for 20%-30% of catches. The Seychelles case study revealed similar total fish biomass on macroalgal and coral reefs, although the biomass of primary target species increased as macroalgae cover expanded. Our findings reinforce that multiple habitat types are needed to support tropical fishery stability and sustainability. Whilst coral habitats have been the focus of tropical fisheries management, we show the potential for macroalgae-associated fish to support catch size and diversity in ways that reduce vulnerability to overfishing. This is pertinent to seascapes where repeated disturbances are facilitating the replacement of coral reef with macroalgal habitats

With(out) a little help from my friends: an IL-12/CD40L-mediated feed-forward loop between CD8+ T cells and DCs

CD40-CD40L interactions are important for both antigen-dependent B-cell differentiation and effector and memory T-cell formation. The prevailing view is that CD40L is expressed on activated CD4(+) T cells, which enables them to provide help to high-affinity B cells in GCs and to license DCs for efficient induction of CD8(+) T-cell responses. Interestingly, CD8(+) T cells themselves can also express CD40L and, in this issue of the European Journal of Immunology, Thiel and colleagues [Eur. J. Immunol. 2013. 43: 1511-1517] show that CD40L expression on these cells can be part of a self-sustaining feed-forward loop, in which expression of CD40L is induced by IL-12 and TCR signaling. This provides a paradigm shift in our thinking about the requirements of effector CD8(+) T-cell development and the role herein of CD4(+) T cells to provide help in this proces

Phenotype and function of human T lymphocyte subsets: consensus and issues

In recent years, a tremendous effort has been devoted to the detailed characterization of the phenotype and function of distinct T cell subpopulations in humans, as well as to their pathway(s) of differentiation and role in immune responses. But these studies seem to have generated more questions than definitive answers. To clarify issues related to the function and differentiation of T cell subsets, one session of the MASIR 2008 conference was dedicated to this topic. Several points of consensus and discord were highlighted in the work presented during this session. We provide here an account of these points, including the relative heterogeneity of T cell subpopulations during infections with distinct pathogens, the relationship between phenotypic and functional T cell attributes, and the pathway(s) of T cell differentiation. Finally, we discuss the problems which still limit general agreemen

Tissue-resident memory T cells at the center of immunity to solid tumors

Immune responses in tissues are constrained by the physiological properties of the tissue involved. Tissue-resident memory T cells (TRM cells) are a recently discovered lineage of T cells specialized for life and function within tissues. Emerging evidence has shown that TRM cells have a special role in the control of solid tumors. A high frequency of TRM cells in tumors correlates with favorable disease progression in patients with cancer, and studies of mice have shown that TRM cells are necessary for optimal immunological control of solid tumors. Here we describe what defines TRM cells as a separate lineage and how these cells are generated. Furthermore, we discuss the properties that allow TRM cells to operate in normal and transformed tissues, as well as implications for the treatment of patients with cancer

Function of CD27 in helper T cell differentiation

Differentiation of naïve CD4(+) T cells to functional effector T-helper (T(H)) cells is driven by both costimulatory molecules and cytokines. Although polarizing cytokines can induce the differentiation into a particular T(H)-subset, certain costimulatory molecules also seem to affect this polarization process. We have previously found that CD70-transgenic (CD70TG) mice develop large numbers of IFN-γ-producing CD4(+) T cells and we therefore questioned whether CD27 triggering provides an instructive signal for T(H)1 differentiation or rather supports T(H) cell formation in general. Although CD70TG mice on a T(H)1-prone C57Bl/6J background develop more T(H)1 cells, we found that this phenotype is lost when CD70TG mice are fully backcrossed on a T(H)2-prone Balb/c background, but is not replaced with more T(H)2 cells. Furthermore, CD70-overexpression is not sufficient to drive T(H)17 cell formation, nor does it affect the generation of FoxP3(+) regulatory T cells. Using an in vitro setting, we found that CD27-triggering does not provide instructive signals for a specific T(H) cell subset, but, depending on the cytokine milieu and genetic background, supports T(H)1 cell formation, while it inhibits the formation of T(H)17 but not T(H)2 cells. Induction of allergic airway inflammation in CD70TG Balb/c mice further illustrates that CD27 plays a supportive role in T(H)1 differentiation in vivo, without modulating the classical T(H)2 response. This supportive role of CD27 in T(H) cell polarization could not be attributed to a specific change of transcription factor expression levels. In summary, this study indicates that CD27 signalling does influence T(H) cell differentiation, but that it is highly dependent on the conditions and genetic backgroun