Bordeaux 2018: Wine, Cheese, and γδ T Cells

The 8th “International conference” was held at the University of Bordeaux, 7–10 June 2018. The lead organizer was Julie Déchanet-Merville who together with the other members of the organizing committee; Maria Mamani Matsuda, Matthias Eberl, Myriam Capone, Lionel Couzi, Hannah Kaminski, Layal Massara, Pierre Merville, Sonia Netzer, Angela Pappalardo, Charlotte Domblides, and Vincent Pitard, provided an interesting and exciting programme covering recent progress and developments in all aspects of γδ T cell research. The conference had a very good attendance with 294 delegates from 28 countries on the five continents (Figure 1). In total, 160 abstracts were submitted; resulting in 57 oral presentations and 103 poster presentations. In addition, eight “special lectures” were given after invitation. A “best poster” and “oral presentations” competition was held, covering all sessions, resulting in 10 and 5 awards, respectively (funded by AAI). Thirty-six travel awards were provided for students and post-docs by generous donations from NIH, European Federation of Immunological Societies and Gamma Delta Therapeutics Inc

REDD+ on the rocks? Conflict over forest and politics of justice in Vietnam

In Vietnam, villagers involved in a REDD+ (reduced emissions from deforestation and forest degradation) pilot protect areas with rocks which have barely a tree on them. The apparent paradox indicates how actual practices differ from general ideas about REDD+ due to ongoing conflict over forest, and how contestations over the meaning of justice are a core element in negotiations over REDD+. We explore these politics of justice by examining how the actors involved in the REDD+ pilot negotiate the particular subjects, dimensions, and authority of justice considered relevant, and show how politics of justice are implicit to practical decisions in project implementation. Contestations over the meaning of justice are an important element in the practices and processes constituting REDD+ at global, national and local levels, challenging uniform definitions of forest justice and how forests ought to be managed

Two distinct populations of Bovine IL-17+ T-cells can be induced and WC1+IL-17+γδ T-cells are effective killers of protozoan parasites

IL-17 has emerged as a key player in the immune system, exhibiting roles in protection from infectious diseases and promoting inflammation in autoimmunity. Initially thought to be CD4 T-cell-derived, the sources of IL-17 are now known to be varied and belong to both the innate and adaptive arms of the immune system. Mechanisms for inducing IL-17 production in lymphoid cells are thought to rely on appropriate antigenic stimulation in the context of TGF-β1, IL-6 and/or IL-1β. Using culture protocols adapted from human studies, we have effectively induced both bovine CD4+ and WC1+ γδ T-cells to produce IL-17 termed Th17 and γδ17 cells, respectively. The negative regulatory effect of IFN-γ on mouse and human IL-17 production can be extended to the bovine model, as addition of IFN-γ decreases IL-17 production in both cell types. Furthermore we show that infection with the protozoan Neospora caninum will induce fibroblasts to secrete pro-IL-17 factors thereby inducing a γδ17 phenotype that preferentially kills infected target cells. Our study identifies two T-cell sources of IL-17, and is the first to demonstrate a protective effect of IL-17+ T-cells in ruminants. Our findings offer further opportunities for future adjuvants or vaccines which could benefit from inducing these responses

TCR signal strength controls thymic differentiation of discrete proinflammatory gamma delta T cell subsets

The mouse thymus produces discrete gd T cell subsets that make either interferon-g (IFN-g) or interleukin 17 (IL-17), but the role of the T cell antigen receptor (TCR) in this developmental process remains controversial. Here we show that Cd3g+/− Cd3d+/− (CD3 double-haploinsufficient (CD3DH)) mice have reduced TCR expression and signaling strength on gd T cells. CD3DH mice had normal numbers and phenotypes of ab thymocyte subsets, but impaired differentiation of fetal Vg6+ (but not Vg4+) IL-17- producing gd T cells and a marked depletion of IFN-g-producing CD122+ NK1.1+ gd T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-g+ gd T cells and were resistant to experimental cerebral malaria. Thus, TCR signal strength within specific thymic developmental windows is a major determinant of the generation of proinflammatory gd T cell subsets and their impact on pathophysiology

Visual, Motor and Attentional Influences on Proprioceptive Contributions to Perception of Hand Path Rectilinearity during Reaching

We examined how proprioceptive contributions to perception of hand path straightness are influenced by visual, motor and attentional sources of performance variability during horizontal planar reaching. Subjects held the handle of a robot that constrained goal-directed movements of the hand to the paths of controlled curvature. Subjects attempted to detect the presence of hand path curvature during both active (subject driven) and passive (robot driven) movements that either required active muscle force production or not. Subjects were less able to discriminate curved from straight paths when actively reaching for a target versus when the robot moved their hand through the same curved paths. This effect was especially evident during robot-driven movements requiring concurrent activation of lengthening but not shortening muscles. Subjects were less likely to report curvature and were more variable in reporting when movements appeared straight in a novel “visual channel” condition previously shown to block adaptive updating of motor commands in response to deviations from a straight-line hand path. Similarly, compromised performance was obtained when subjects simultaneously performed a distracting secondary task (key pressing with the contralateral hand). The effects compounded when these last two treatments were combined. It is concluded that environmental, intrinsic and attentional factors all impact the ability to detect deviations from a rectilinear hand path during goal-directed movement by decreasing proprioceptive contributions to limb state estimation. In contrast, response variability increased only in experimental conditions thought to impose additional attentional demands on the observer. Implications of these results for perception and other sensorimotor behaviors are discussed

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

Epigenetic and transcriptional signatures of stable versus plastic differentiation of proinflammatory gd T cell subsets

Two distinct subsets of γδ T cells that produce interleukin 17 (IL-17) (CD27(-) γδ T cells) or interferon-γ (IFN-γ) (CD27(+) γδ T cells) develop in the mouse thymus, but the molecular determinants of their functional potential in the periphery remain unknown. Here we conducted a genome-wide characterization of the methylation patterns of histone H3, along with analysis of mRNA encoding transcription factors, to identify the regulatory networks of peripheral IFN-γ-producing or IL-17-producing γδ T cell subsets in vivo. We found that CD27(+) γδ T cells were committed to the expression of Ifng but not Il17, whereas CD27(-) γδ T cells displayed permissive chromatin configurations at loci encoding both cytokines and their regulatory transcription factors and differentiated into cells that produced both IL-17 and IFN-γ in a tumor microenvironment

Institutions and governance of communal rangelands in South Africa

The creation of local institutions with a mandate over land access and control is seen as a prerequisite for successful decentralisation of land tenure and effective local resource management in sub-Saharan Africa. However, with land tenure reform in South Africa currently at a state of legislative impasse, real uncertainty now exists over land rights and governance of rangeland in many communal areas. This paper draws on case study material from Eastern Cape province to illustrate how this ongoing uncertainty has resulted in the operation of a range of traditional authority and civil society institutions in different communal areas with varying degrees of legitimate authority over land administration and highly variable performance in managing rangeland resources. Collective management of rangeland resources seems most difficult in environments where land rights are contested because of the coexistence of traditional leaders and civil society institutions. On this basis an approach to tenure reform is advocated, which vests all powers over local land administration in democratically elected and accountable civil society institutions. Some successful examples of this already exist and might serve to guide policy formation, which must be flexible enough to accommodate collective management approaches that emphasise cooperation both within and between communities.Keywords: common property, land tenure, natural resource management, traditional leadersAfrican Journal of Range & Forage Science 2013, 30(1&2): 77–8