Cutting edge: is vasoactive intestinal peptide a type 2 cytokine?

A component of the chemical language shared by the immune and nervous system is the expression of neuropeptides by immune cells. Vasoactive intestinal peptide (VIP) was shown to be produced by T lymphocytes. Here we investigate whether T cell subsets differentially express VIP. Our studies indicate that, upon specific Ag stimulation, Th2 and T2 cells, but not Th1 and T1 cells derived from TCR transgenic (Tg) mice, express VIP mRNA and protein, and secrete VIP. Following immunization with the specific Ag, significant levels of VIP are present in the serum of syngeneic, non-Tg hosts that receive Th2, but not Th1 Tg cells. Th2 Tg cells recovered from the non-Tg hosts immunized with the specific Ag, but not with an irrelevant Ag, express intracellular VIP. Because VIP is produced by Ag-stimulated type 2 T cells, and differentially affects Th1 and Th2 cells, could VIP be viewed as a type 2 cytokine?     

Cutting edge: tubulin α functions as an adaptor in NFAT-importin β interaction

Upon T cell stimulation, NFAT is dephosphorylated by calcineurin, leading to nuclear translocation via NFAT-importin β interaction. Whereas the process of NFAT dephosphorylation has been well researched, the molecular mechanism of NFAT-importin β interaction remains unknown. In contrast to NF-κB and STAT, no importin α family members have been reported as adaptor proteins for NFAT. Our study shows that tubulin α, but not tubulin β, binds to the N-terminal region of NFAT containing the regulatory and Rel homology domains. Importin β interacts with the NFAT-tubulin α complex rather than NFAT or tubulin α alone, resulting in cotranslocation of NFAT and tubulin α into the nucleus. Furthermore, the interaction is suppressed by acetate-induced tubulin α acetylation at lysine 40. In conclusion, tubulin α functions as an adaptor in NFAT-importin β interaction, and this function is regulated by acetate-induced acetylation.     

Cutting edge: activation of virus-specific CD4 T cells throughout γ-herpesvirus latency

CD4 T cells are essential for immune control of γ-herpesvirus latency. We previously identified a murine MHC class II-restricted epitope in γ-herpesvirus-68 gp150 (gp150(67-83)I-A(b)) that elicits CD4 T cells that are maintained throughout long-term infection. However, it is unknown whether naive cells can be recruited into the antiviral CD4 T cell pool during latency. In this study, we generate a mouse transgenic for a gp150-specific TCR and show epitope-specific activation of transgenic CD4 T cells during acute and latent infections. Furthermore, although only dendritic cells can stimulate virus-specific CD8 T cells during latency, we show that both dendritic cells and B cells stimulate transgenic CD4 T cells. These studies demonstrate that naive CD4 T cells specific for a viral glycoprotein can be stimulated throughout infection, even during quiescent latency, suggesting that CD4 T cell memory is maintained in part by the continual recruitment of naive cells.     

IFN-α and TRAIL: A double edge sword in HIV-1 disease?

IFN-α is rapidly upregulated in response to viral infections and it is an essential player in innate immunity against viruses. pDCs are the most potent IFN-α-producing cells and serve as an essential link between innate and adaptive immunity. The fate of pDCs in the course of HIV-1 infection is still a matter of debate, and the question of the detrimental role of chronic production of IFN-α remains open. In particular, IFN-α has been shown to induce the expression of the death ligand TRAIL on pDCs, transforming them into killer pDCs that may contribute to the destruction of CD4(+) T cells, the hallmark of HIV-1-induced disease. In this review, we discuss our current understanding of the protective and pathogenic roles of both IFN-α and TRAIL in HIV-1 disease.     

Inbreeding at the edge: does inbreeding depression increase under more stressful conditions?

Edge populations are frequently small and subject to stressful conditions that may compromise their long‐term viability. Inbreeding can play an important role in small populations by reducing genetic diversity, leading to the fixation of deleterious mutations and, finally, carrying populations to an extinction vortex through inbreeding depression. Although stressful conditions may enhance the intensity of inbreeding depression, evidence to date is inconclusive in marginal habitats. Local adaptation, promoting native genotypes, and gene flow, reducing allele fixation, are two factors that can have different effects on the intensity of inbreeding depression. Three populations of Silene ciliata distributed across an elevation gradient at the southernmost edge of the species distribution were used for this study. Several fitness components – germination, survival and growth rate – were compared between inbred seedlings and seedlings from within‐ and between‐population outcrosses, both in the field and controlled conditions. Overall, inbred seedlings had lower fitness than outcrossed seedlings. For most of the variables analysed, similar inbreeding depression effects were found in all three populations, but, for seed weight and seedling survival curve, inbreeding depression was only found in the low altitude population. Similarly, inbreeding depression was more evident in the field than in controlled chamber conditions. Outcrosses between populations contributed to an increase in most fitness estimates and populations, suggesting that the benefits of reducing inbreeding depression overrode the potentially deleterious effects of disrupting local adaptation. Our results suggest that inbreeding depression plays an important role in the fitness of early life stages of Silene ciliata at its southernmost distribution limit, but only provided partial support to the hypothesis that stressful conditions enhance the expression of inbreeding depression.     

Conserving butterflies in fragmented plantation forests: are edge and interior habitats equally important?

Edge effects are increasing in forest-dominated landscapes worldwide, due to increased fragmentation by other land uses. Understanding how species respond to edges is therefore critical to define adequate conservation measures. We compared the relative importance of interior and edge habitats for butterflies in a landscape composed of even-aged pine plantations interspersed with semi-natural habitats. Butterfly assemblages were surveyed simultaneously at the edge and the interior of 68 patches belonging to four main habitat types: herbaceous firebreaks, clearcuts and young pine stands, older pine stands, and deciduous woodlands. Butterfly species richness was higher at edges than in interior habitats, especially for pine stands. Assemblage composition differed significantly between edge and interior habitats, except for firebreaks. Of the 23 most abundant butterfly species, seven were significantly more abundant in one or all edge habitat types, five in interior habitats, and 11 species showed no edge-interior preference. Modelling the presence of individual species in edge habitats revealed the importance of habitat variables such as the abundance of nectar and host-plants, but also of the abundance of the same species in the adjacent interior habitat. Moreover, our results suggest that most species use several, different habitat types to find supplementary or complementary resources, including micro-climatic refuges to escape hot temperatures during summer. The use of adjacent edge and interior habitats by butterflies is probably a key process in such mosaic landscapes and underlines the importance of landscape heterogeneity for butterfly conservation.     

Quantifying avoided deforestation in Pará: Protected areas,buffer zones and edge effects

Percentage of forests saved due to establishment of protected areas is an important piece of information for government institutions and, therefore, is the goal of this study. However, non random location selection bias makes such information directly unobservable. To overcome this problem, propensity score matching was applied. Unlike in previous studies, impact of buffer zone management was assessed by estimating avoided deforestation in buffer zones and park edges. The study area is the state of Pará. Overall results revealed that park protection saved 0.72% of protected surface from deforestation during 2000–2004 year period (∼2900 km² of forests). The highest percentage of avoided deforestation was recorded in protected areas, situated near deforestation hotspots: central part of Eastern Pará, alongside Trans-Amazonian highway and on the banks of Amazon River. The findings also suggest that buffer zones tend to reduce deforestation where pressure on forests is lower, but substitution effect takes over in areas of high deforestation pressure (since loggers are prevented from deforesting within conservation units, deforestation in surrounding areas increases). Finally, the study does not find evidence of edge effects in the state of Pará.     

Cutting edge: Intrinsic programming of thymic γδT cells for specific peripheral tissue localization

Various innate-like T cell subsets preferentially reside in specific epithelial tissues as the first line of defense. However, mechanisms regulating their tissue-specific development are poorly understood. Using the prototypical skin intraepithelial γδT cells (sIELs) as a model, we show in this study that a TCR-mediated selection plays an important role in promoting acquisition of a specific skin-homing property by fetal thymic sIEL precursors for their epidermal location, and the skin-homing potential is intrinsically programmed even before the selection. In addition, once localized in the skin, the sIEL precursors develop into sIELs without the requirement of further TCR-ligand interaction. These studies reveal that development of the tissue-specific lymphocytes is a hard-wired process that targets them to specific tissues for proper functions.     

Does self-organized criticality drive leading edge protrusion?

Arp2/3 complex nucleates dendritic actin networks and plays a pivotal role in the formation of lamellipodia at the leading edge of motile cells. Mouse fibroblasts lacking functional Arp2/3 complex have the characteristic smooth, veil-like lamellipodial leading edge of wild-type cells replaced by a massive, bifurcating filopodia-like protrusions (FLPs) with fractal geometry. The nanometer-scale actin-network organization of these FLPs can be linked to the fractal geometry of the cell boundary by a self-organized criticality through the bifurcation behavior of cross-linked actin bundles. Despite the pivotal role of the Arp2/3 complex in cell migration, the cells lacking functional Arp2/3 complex migrate at rates similar to wild-type cells. However, these cells display defects in the persistence of a directional movement. We suggest that Arp2/3 complex suppresses the formation of FLPs by locally fine-tuning actin networks and favoring dendritic geometry over bifurcating bundles, giving cells a distinct evolutionary edge by providing the means for a directed movement.     

Experimental effects of habitat fragmentation on rove beetles and ants: patch area or edge?

The effects of habitat fragmentation may include the loss of species from isolated fragments or changes in species abundances among habitats that differ in area, structure, or edge characteristics. We measured the species richness and abundance of ground‐dwelling insects in a 1.14‐ha old field that was mowed to produce patches of unmowed vegetation which differed in size, degree of isolation, and the amount of habitat edge. Four treatments – ranging from unfragmented (169‐m²) to highly fragmented (1‐m²) patches – were replicated four times in a Latin square design, and insects were sampled twice during 1995 using 177 pitfall traps. Species richness showed a non‐monotonic response to fragmentation, with the fewest species occurring in the slightly fragmented treatment. Responses of rove beetles and ants, the most species‐rich and abundant taxa, respectively, were similar to the overall insect community but ants had a stronger and more consistent treatment effect in both sample months. Ordinations of ant and rove‐beetle assemblages using nonmetric multidimensional scaling showed that the slightly fragmented treatment differed from other treatments in species occurrence and abundance. The lower species richness in the slightly fragmented treatment was primarily due to a subset of ant and rove beetle species that showed a lower abundance than in other treatments, possibly because this treatment had the greatest amount of habitat edge. We hypothesize that the non‐monotonic species response to fragmentation was due to the differential effects of habitat edge on species movements across the habitat boundary between unmowed patches and mowed areas. A greater effect due to the amount of habitat edge rather than total patch area, at least among the range of patch sizes studied, suggests that the length of habitat edge may be quite important to the distribution and abundance of ground‐dwelling animals in fragmented habitats.     

Cutting edge: immune cells as sources and targets of the IL-10 family members?

This study investigated the expression of five novel human IL-10-related molecules and their receptors in blood mononuclear cells. IL-19 and IL-20 were found to be preferentially expressed in monocytes. IL-22 and IL-26 (AK155) expression was exclusively detected in T cells, especially upon type 1 polarization, and in NK cells. IL-24 (melanoma differentiation-associated gene 7) expression was restricted to monocytes and T cells. Detection of these molecules in lymphocytes was predominantly linked to cellular activation. Regarding T cells, IL-26 was primarily produced by memory cells, and its expression was independent on costimulation. In contrast to the high expression of receptors for IL-10 homologs in different tissues and cell lines, monocytes and NK, B, and T cells showed clear expression only of IL-10R1, IL-10R2, and IL-20R2. In these cells, IL-20R2 might be part of a still-unknown receptor complex. Therefore, immune cells may represent a major source but a minor target of the novel IL-10 family members.