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Scooped by
Gilbert C FAURE
February 13, 2018 11:26 AM
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Malarial infection in naive individuals induces a robust innate immune response. In the recently described model of innate immune memory, an initial stimulus primes the innate immune system to either hyperrespond (termed training) or hyporespond (tolerance) to subsequent immune challenge. Previous work in both mice and humans demonstrated that infection with malaria can both serve as a priming stimulus and promote tolerance to subsequent infection. In this study, we demonstrate that initial stimulation with Plasmodium falciparum –infected RBCs or the malaria crystal hemozoin induced human adherent PBMCs to hyperrespond to subsequent ligation of TLR2. This hyperresponsiveness correlated with increased H3K4me3 at important immunometabolic promoters, and these epigenetic modifications were also seen in Kenyan children naturally infected with malaria. However, the use of epigenetic and metabolic inhibitors indicated that the induction of trained immunity by malaria and its ligands may occur via a previously unrecognized mechanism(s).
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Scooped by
Gilbert C FAURE
February 8, 2018 2:40 PM
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There's no escaping norovirus when you have it—the symptoms from this gastroenteritis-causing virus, though brief, are often debilitating. Preventing infections will rely on improving our understanding of how norovirus enters host cells. Orchard et al. show that the entry of murine norovirus (MNoV) into host cells requires a protein called CD300lf. In cell culture, mouse cells needed to express CD300lf in order for MNoV binding, entry, and replication to occur. Deleting the gene encoding CD300lf in mice protected them against MNoV infection. Human cells expressing CD300lf allowed MNoV to break the species barrier, a finding that may lead to new insights into the infectivity of this virus.
Science , this issue p. [933][1]
[1]: /lookup/doi/10.1126/science.aaf1220
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Scooped by
Gilbert C FAURE
February 7, 2018 11:03 AM
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Activated B cells can initially differentiate into three functionally distinct fates—early plasmablasts (PBs), germinal center (GC) B cells, or early memory B cells—by mechanisms that remain poorly understood. Here, we identify atypical chemokine receptor 4 (ACKR4), a decoy receptor that binds and degrades CCR7 ligands CCL19/CCL21, as a regulator of early activated B cell differentiation. By restricting initial access to splenic interfollicular zones (IFZs), ACKR4 limits the early proliferation of activated B cells, reducing the numbers available for subsequent differentiation. Consequently, ACKR4 deficiency enhanced early PB and GC B cell responses in a CCL19/CCL21-dependent and B cell–intrinsic manner. Conversely, aberrant localization of ACKR4-deficient activated B cells to the IFZ was associated with their preferential commitment to the early PB linage. Our results reveal a regulatory mechanism of B cell trafficking via an atypical chemokine receptor that shapes activated B cell fate.
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Suggested by
LIGHTING
February 5, 2018 9:38 AM
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Luo et al. show that CD40 and BCR signaling in GC B cells is rewired to control very
different pathways, and both signals are required for optimal induction of c-Myc,
suggesting a mechanism of signaling-directed positive selection of GC B cells.
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Scooped by
Gilbert C FAURE
February 4, 2018 3:49 AM
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How is the cellular composition of a tissue stably maintained?
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Suggested by
Société Francaise d'Immunologie
February 1, 2018 3:14 PM
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“Fundamental immunodeficiency” is the inability of the encoded immune system to protect an otherwise healthy host from every infection that could threaten its life. In contrast to primary immunodeficiencies, fundamental immunodeficiency is not rare but nearly universal. It results not from variation in a given host gene but from the rate and extent of variation in the genes of other organisms. The remedy for fundamental immunodeficiency is “adopted immunity,” not to be confused with adaptive or adoptive immunity. Adopted immunity arises from four critical societal contributions to the survival of the human species: sanitation, nutrition, vaccines, and antimicrobial agents. Immunologists have a great deal to contribute to the development of vaccines and antimicrobial agents, but they have focused chiefly on vaccines, and vaccinology is thriving. In contrast, the effect of antimicrobial agents in adopted immunity, although fundamental, is fragile and failing. Immunologists can aid the development of sorely needed antimicrobial agents, and the study of antimicrobial agents can help immunologists discover targets and mechanisms of host immunity.
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Scooped by
Gilbert C FAURE
February 1, 2018 1:56 AM
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Scooped by
Gilbert C FAURE
January 30, 2018 1:44 PM
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Hidden genetic effects behind immune diseases may be missed, study suggests
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Scooped by
Gilbert C FAURE
January 29, 2018 11:46 AM
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The mammalian T cell receptor (TCR) orchestrates immunity by responding to many billions of different ligands that it has never encountered before and cannot adapt to at the protein sequence level
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Suggested by
Société Francaise d'Immunologie
January 29, 2018 5:10 AM
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Type I natural killer T (NKT) cells are innate-like T lymphocytes that recognize glycolipid antigens presented by the MHC class I-like protein CD1d. Agonistic activation of NKT cells leads to rapid pro-inflammatory and immune modulatory cytokine and chemokine responses. This property of NKT cells, in conjunction with their interactions with antigen-presenting cells, controls downstream innate and adaptive immune responses against cancers and infectious diseases, as well as in several inflammatory disorders. NKT cell properties are acquired during development in the thymus and by interactions with the host microbial consortium in the gut, the nature of which can be influenced by NKT cells. This latter property, together with the role of the host microbiota in cancer therapy, necessitates a new perspective. Hence, this review provides an initial approach to understanding NKT cells from an ecological evolutionary developmental biology (eco-evo-devo) perspective.
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Suggested by
Société Francaise d'Immunologie
January 28, 2018 6:42 AM
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An increased understanding of infant antibody responses to RSV infection would greatly
facilitate vaccine development. Goodwin et al. isolate and structurally characterize
antibodies from RSV-infected infants and identify potent neutralizing antibodies that
lack somatic hypermutation. The results provide a framework for the rational design
of age-specific RSV vaccines.
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Scooped by
Gilbert C FAURE
January 22, 2018 6:23 AM
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Scooped by
Gilbert C FAURE
January 21, 2018 11:36 AM
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Special collection on cell death
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Scooped by
Gilbert C FAURE
February 12, 2018 1:14 PM
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For a long time, immunologists have believed that classical CD4+ and CD8+ T cells recognize peptides (referred to as epitopes), derived from protein antigens presented by MHC/HLA class I or II. Ove
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Scooped by
Gilbert C FAURE
February 8, 2018 11:14 AM
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The molecular and cellular biology of thymic epithelial cells (TECs) often relies on the analysis of TECs isolated in enzymatically digested single-cell suspensions derived from mouse thymus. Many independent studies have reported that the estimated cellularity of total TECs isolated from one adult mouse is on the order of up to 105. However, these numbers appear extremely small given that the cellularity of total thymocytes exceeds 108 and that TECs play multiple roles in thymocyte development and repertoire formation. In the present study, we aimed to measure the numbers of β5t-expressing cortical TECs and Aire-expressing medullary TECs in postnatal mouse thymus in situ without enzymatic digestion. The numbers of these TECs were manually counted in individual thymic sections and were three-dimensionally summed throughout the entire thymic lobes. The results show that the cellularity of total TECs in one 5-wk-old female mouse exceeds 106, containing ∼9 × 105 β5t+ cortical TECs and ∼1.1 × 106 Aire+ medullary TECs. These results suggest that the use of conventional enzymatic digestion methods for the isolation of TECs may have resulted in the underestimation of the cellularity, and possibly the biology, of TECs.
This article is featured in In This Issue , p.[1231][1]
[1]: /lookup/volpage/200/1231
The functional capacities of natural killer (NK) cells differ within and between individuals,
reflecting considerable genetic variation. ‘Licensing/arming’, ‘disarming’, and ‘tuning’
are models that have been proposed to explain how interactions between MHC class I
molecules and their cognate inhibitory receptors – Ly49 in mice and KIR in humans
– ‘educate’ NK cells for variable reactivity and sensitivity to inhibition. In this
review we discuss recent progress toward understanding the genetic, epigenetic, and
molecular features that titrate NK effector function and inhibition, and the impact
of variable NK cell education on human health and disease.
Via Krishan Maggon
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Scooped by
Gilbert C FAURE
February 4, 2018 1:35 PM
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Milwaukee, WI (PRWEB) February 02, 2018 -- The Clinical Immunology Society (CIS) announces its newly instituted foundation. The CIS Foundation was created to
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Scooped by
Gilbert C FAURE
February 3, 2018 1:02 PM
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FOXP3‐expressing CD4+ T regulatory (Treg) cells are instrumental for the maintenance of self‐tolerance. They are also involved in the prevention of allergy, allograft rejection, foetal rejectio
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Scooped by
Gilbert C FAURE
February 1, 2018 6:47 AM
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Suggested by
LIGHTING
January 31, 2018 2:20 PM
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The S100 proteins, a family of calcium-binding cytosolic proteins, have a broad range of intracellular and extracellular functions through regulating calcium balance, cell apoptosis, migration, proliferation, differentiation, energy metabolism, and inflammation. The intracellular functions of S100 proteins involve interaction with intracellular receptors, membrane protein recruitment/transportation, transcriptional regulation and integrating with enzymes or nucleic acids and DNA repair. The S100 proteins could also be released from the cytoplasm, induced by tissue/cell damage and cellular stress. The extracellular S100 proteins, serving as a danger signal, are crucial in regulating immune homeostasis, post-traumatic injury, and inflammation. Extracellular S100 proteins are also considered biomarkers for some specific diseases. In this review, we will discuss the multi-functional roles of S100 proteins, especially their potential roles associated with cell migration, differentiation, tissue repair and inflammation.
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Suggested by
LIGHTING
January 30, 2018 8:44 AM
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Suggested by
Société Francaise d'Immunologie
January 29, 2018 5:10 AM
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The molecular bases of repressive transcriptional mechanisms contributing to macrophage polarization are not well understood. Czimmerer et al. show that in alternatively polarized macrophages, IL-4-activated STAT6 represses a large set of enhancers modulating
the transcriptional program. STAT6-repressed enhancers are characterized by reduced chromatin accessibility, eRNA expression, LDTF, and p300 binding. IL-4-STAT6-mediated repression limits the inflammatory responsiveness including inflammasome activation,
IL-1β production, and pyroptosis. Thus, the IL4-STAT6 pathway establishes an epigenomic signature to selectively repress the macrophage inflammation program.
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Scooped by
Gilbert C FAURE
January 28, 2018 7:15 AM
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Following activation, T cells rapidly divide and acquire effector functions. This energetically demanding process depends upon the ability of T cells to undergo metabolic remodeling from oxidative phosphorylation to aerobic glycolysis, during which glucose is converted into lactate and released extracellularly. In this article, we demonstrate that extracellular lactate can be used to dynamically assess human T cell responses in vitro. Extracellular lactate levels strongly correlated with T cell proliferation, and measuring lactate compared favorably with traditional methods for determining T cell responses (i.e., [3H]thymidine incorporation and the use of cell proliferation dyes). Furthermore, we demonstrate the usefulness of measuring lactate as a read-out in conventional suppression assays and high-throughput peptide-screening assays. Extracellular lactate was stably produced over 7 d, and results were reproducibly performed over several freeze–thaw cycles. We conclude that the use of extracellular lactate measurements can be a sensitive, safe, stable, and easy-to-implement research tool for measuring T cell responses and cellular metabolic changes in vitro.
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Scooped by
Gilbert C FAURE
January 23, 2018 2:17 AM
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Scooped by
Gilbert C FAURE
January 21, 2018 11:37 AM
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