IL-10 Suppression of NK/DC Crosstalk Leads to Poor Priming of MCMV-Specific CD4 T Cells and Prolonged MCMV Persistence

IL-10 is an anti-inflammatory cytokine that regulates the extent of host immunity to infection by exerting suppressive effects on different cell types. Herpes viruses induce IL-10 to modulate the virus-host balance towards their own benefit, resulting in prolonged virus persistence. To define the cellular and molecular players involved in IL-10 modulation of herpes virus-specific immunity, we studied mouse cytomegalovirus (MCMV) infection. Here we demonstrate that IL-10 specifically curtails the MCMV-specific CD4 T cell response by suppressing the bidirectional crosstalk between NK cells and myeloid dendritic cells (DCs). In absence of IL-10, NK cells licensed DCs to effectively prime MCMV-specific CD4 T cells and we defined the pro-inflammatory cytokines IL-12, IFN-γ and TNF-α as well as NK cell activating receptors NKG2D and NCR-1 to regulate this bidirectional NK/DC interplay. Consequently, markedly enhanced priming of MCMV-specific CD4 T cells in Il10-/-mice led to faster control of lytic viral replication, bu

Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7

Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF-7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells

Regulation of immunity during visceral Leishmania infection

Unicellular eukaryotes of the genus Leishmania are collectively responsible for a heterogeneous group of diseases known as leishmaniasis. The visceral form of leishmaniasis, caused by L. donovani or L. infantum, is a devastating condition, claiming 20,000 to 40,000 lives annually, with particular incidence in some of the poorest regions of the world. Immunity to Leishmania depends on the development of protective type I immune responses capable of activating infected phagocytes to kill intracellular amastigotes. However, despite the induction of protective responses, disease progresses due to a multitude of factors that impede an optimal response. These include the action of suppressive cytokines, exhaustion of specific T cells, loss of lymphoid tissue architecture and a defective humoral response. We will review how these responses are orchestrated during the course of infection, including both early and chronic stages, focusing on the spleen and the liver, which are the main target organs of visceral Leishmania in the host. A comprehensive understanding of the immune events that occur during visceral Leishmania infection is crucial for the implementation of immunotherapeutic approaches that complement the current anti-Leishmania chemotherapy and the development of effective vaccines to prevent disease.The research leading to these results has received funding from the European Community’s Seventh Framework Programme under grant agreement No.602773 (Project KINDRED). VR is supported by a post-doctoral fellowship granted by the KINDReD consortium. RS thanks the Foundation for Science and Technology (FCT) for an Investigator Grant (IF/00021/2014). This work was supported by grants to JE from ANR (LEISH-APO, France), Partenariat Hubert Curien (PHC) (program Volubilis, MA/11/262). JE acknowledges the support of the Canada Research Chair Program

Validation of quantitative trait loci for aluminum tolerance in Chinese wheat landrace FSW

Citation: Dai, J., Bai, G., Zhang, D. et al. Euphytica (2013) 192: 171. https://doi.org/10.1007/s10681-012-0807-9Aluminum (Al) toxicity is one of the major constraints for wheat production in acidic soils worldwide and use of Al-tolerant cultivars is one of the most effective approaches to reduce Al damage in the acidic soils. A Chinese landrace, FSW, shows a high level of tolerance to Al toxicity and a mapping population of recombinant inbred lines (RILs) was developed from a cross between FSW and Al-sensitive US spring wheat cultivar Wheaton to validate the quantitative trait loci (QTL) previously identified in FSW. The mapping population was evaluated for net root growth (NRG) during Al stress in a nutrient solution culture and hematoxylin staining score (HSS) of root tips after Al stress. After 132 simple sequence repeat (SSR) markers from three chromosomes that were previously reported to have the QTLs were analyzed in the population, two QTLs for Al tolerance from FSW were confirmed. The major QTL on chromosome 4DL co-segregated with the Al-activated malate transporter gene (ALMT1), however, sequence analysis of the promoter region (Ups4) of ALMT1 gene indicated that FSW contained a marker allele that is different from the one that was reported to condition Al tolerance in the Brazilian source. Another QTL on chromosome 3BL showed a minor effect on Al tolerance in the population. The two QTLs accounted for about 74.9% of the phenotypic variation for HSS and 72.1% for NRG and demonstrated an epistatic effect for both HSS and NRG. SSR markers closely linked to the QTLs have potential to be used for marker-assisted selection (MAS) to improve Al tolerance in wheat breeding programs