Photoperiod and metabolic health: evidence, mechanism, and implications.

Circadian rhythms are evolutionarily programmed biological rhythms that are primarily entrained by the light cycle. Disruption of circadian rhythms is an important risk factor for several metabolic disorders. Photoperiod is defined as total duration of light exposure in a day.

Extracellular traps are evident in Romanowsky-stained smears of bronchoalveolar lavage from children with non-cystic fibrosis bronchiectasis.

Background And Objective: The importance of extracellular traps (ETs) in chronic respiratory conditions is increasingly recognized but their role in paediatric bronchiectasis is poorly understood. The specialized techniques currently required to study ETs preclude routine clinical use. A simple and cost-effective ETs detection method is needed to support diagnostic applications.

Increased circulating myeloid-derived suppressor cells in vivax malaria and severe falciparum malaria.

Background: Circulating myeloid-derived-suppressor-cells (MDSC) with immunosuppressive function are increased in human experimental Plasmodium falciparum infection, but have not been studied in clinical malaria.

Methods: Using flow-cytometry, circulating polymorphonuclear-MDSC were evaluated in cryopreserved samples from patients with uncomplicated Plasmodium vivax (n = 8) and uncomplicated (n = 4) and severe (n = 16) falciparum malaria from Papua, Indonesia.

Results: The absolute number of circulating polymorphonuclear-MDSC were significantly elevated in severe falciparum malaria patients compared to controls (n = 10).

Age-dependent changes in circulating Tfh cells influence development of functional malaria antibodies in children.

T-follicular helper (Tfh) cells are key drivers of antibodies that protect from malaria. However, little is known regarding the host and parasite factors that influence Tfh and functional antibody development. Here, we use samples from a large cross-sectional study of children residing in an area of high malaria transmission in Uganda to characterize Tfh cells and functional antibodies to multiple parasites stages.

Adults with Plasmodium falciparum malaria have higher magnitude and quality of circulating T-follicular helper cells compared to children.

Background: Protective malarial antibodies are acquired more rapidly in adults than children, independently of cumulative exposure, however the cellular responses mediating these differences are unknown. CD4 T-follicular helper (Tfh) cells have key roles in inducing antibodies, with Th2-Tfh cell activation associated with antibody development in malaria. Whether Tfh cell activation in malaria is age dependent is unknown and no studies have compared Tfh cell activation in children and adults with malaria.

Evaluation of splenic accumulation and colocalization of immature reticulocytes and Plasmodium vivax in asymptomatic malaria: A prospective human splenectomy study.

Background: A very large biomass of intact asexual-stage malaria parasites accumulates in the spleen of asymptomatic human individuals infected with Plasmodium vivax. The mechanisms underlying this intense tropism are not clear. We hypothesised that immature reticulocytes, in which P.

A population of CD4CD38 T cells correlates with disease severity in patients with acute malaria.

Objective: CD4 T cells are critical mediators of immunity to spp. infection, but their characteristics during malarial episodes and immunopathology in naturally infected adults are poorly defined. Flow cytometric analysis of PBMCs from patients with either or malaria revealed a pronounced population of CD4 T cells co-expressing very high levels of CD4 and CD38 we have termed CD4CD38 T cells.

Antiphosphatidylserine Immunoglobulin M and Immunoglobulin G Antibodies Are Higher in Vivax Than Falciparum Malaria, and Associated With Early Anemia in Both Species.

Background: Anemia is a major complication of vivax malaria. Antiphosphatidylserine (PS) antibodies generated during falciparum malaria mediate phagocytosis of uninfected red blood cells that expose PS and have been linked to late malarial anemia. However, their role in anemia from non-falciparum Plasmodium species is not known, nor their role in early anemia from falciparum malaria.

Dysregulated IL-1β-GM-CSF Axis in Acute Rheumatic Fever That Is Limited by Hydroxychloroquine.

Background: Acute rheumatic fever (ARF) and rheumatic heart disease are autoimmune consequences of group A streptococcus infection and remain major causes of cardiovascular morbidity and mortality around the world. Improved treatment has been stymied by gaps in understanding key steps in the immunopathogenesis of ARF and rheumatic heart disease. This study aimed to identify (1) effector T cell cytokine(s) that might be dysregulated in the autoimmune response of patients with ARF by group A streptococcus, and (2) an immunomodulatory agent that suppresses this response and could be clinically translatable to high-risk patients with ARF.

Circulating Neutrophil Extracellular Traps and Neutrophil Activation Are Increased in Proportion to Disease Severity in Human Malaria.

Background: Neutrophil activation results in Plasmodium parasite killing in vitro, but neutrophil products including neutrophil extracellular traps (NETs) mediate host organ damage and may contribute to severe malaria. The role of NETs in the pathogenesis of severe malaria has not been examined.

Methods: In Papua, Indonesia, we enrolled adults with symptomatic Plasmodium falciparum (n = 47 uncomplicated, n = 8 severe), Plasmodium vivax (n = 37), or Plasmodium malariae (n = 14) malaria; asymptomatic P falciparum (n = 19) or P vivax (n = 21) parasitemia; and healthy adults (n = 23) without parasitemia.

Plasmodium falciparum Activates CD16+ Dendritic Cells to Produce Tumor Necrosis Factor and Interleukin-10 in Subpatent Malaria.

Background: The malaria causing parasite Plasmodium subverts host immune responses by several strategies including the modulation of dendritic cells (DCs).

Methods: In this study, we show that Plasmodium falciparum skewed CD16+ DC cytokine responses towards interleukin (IL)-10 production in vitro, distinct to the cytokine profile induced by Toll-like receptor ligation. To determine CD16+ DC responsiveness in vivo, we assessed their function after induced P falciparum infection in malaria-naive volunteers.

Platelets kill circulating parasites of all major species in human malaria.

Platelets are understood to assist host innate immune responses against infection, although direct evidence of this function in any human disease, including malaria, is unknown. Here we characterized platelet-erythrocyte interactions by microscopy and flow cytometry in patients with malaria naturally infected with , , , or Blood samples from 376 participants were collected from malaria-endemic areas of Papua, Indonesia, and Sabah, Malaysia. Platelets were observed binding directly with and killing intraerythrocytic parasites of each of the species studied, particularly mature stages, and was greatest in patients.

Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation.

Plasmacytoid dendritic cells (pDC) are activators of innate and adaptive immune responses that express HLA-DR, toll-like receptor (TLR) 7, TLR9 and produce type I interferons. The role of human pDC in malaria remains poorly characterised. pDC activation and cytokine production were assessed in 59 malaria-naive volunteers during experimental infection with 150 or 1,800 P.

Early Immune Regulatory Changes in a Primary Controlled Human Plasmodium vivax Infection: CD1c Myeloid Dendritic Cell Maturation Arrest, Induction of the Kynurenine Pathway, and Regulatory T Cell Activation.

malaria remains a major public health problem. The requirements for acquisition of protective immunity to the species are not clear. Dendritic cells (DC) are essential for immune cell priming but also perform immune regulatory functions, along with regulatory T cells (Treg).

Vaccination with Altered Peptide Ligands of a Circumsporozoite Protein CD8 T-Cell Epitope: A Model to Generate T Cells Resistant to Immune Interference by Polymorphic Epitopes.

Many pathogens, including the malaria parasite , display high levels of polymorphism within T-cell epitope regions of proteins associated with protective immunity. The T-cell epitope variants are often non-cross-reactive. Herein, we show in a murine model, which modifies a protective CD8 T-cell epitope from the circumsporozoite protein (CS) of (SYIPSAEKI), that simultaneous or sequential co-stimulation with two of its putative similarly non-cross-reactive altered peptide ligand (APL) epitopes (SYIPSAEDI or SYIPSAEAI) has radically different effects on immunity.

Characterization of blood dendritic and regulatory T cells in asymptomatic adults with sub-microscopic Plasmodium falciparum or Plasmodium vivax infection.

Background: Plasmodium falciparum and Plasmodium vivax infections compromise dendritic cell (DC) function and expand regulatory T (Treg) cells in both clinical disease (malaria) and experimental human sub-microscopic infection. Conversely, in asymptomatic microscopy-positive (patent) P. falciparum or P.

Profoundly Reduced CD1c+ Myeloid Dendritic Cell HLA-DR and CD86 Expression and Increased Tumor Necrosis Factor Production in Experimental Human Blood-Stage Malaria Infection.

Dendritic cells (DCs) are sentinels of the immune system that uniquely prime naive cells and initiate adaptive immune responses. CD1c (BDCA-1) myeloid DCs (CD1c(+) mDCs) highly express HLA-DR, have a broad Toll-like receptor (TLR) repertoire, and secrete immune modulatory cytokines. To better understand immune responses to malaria, CD1c(+) mDC maturation and cytokine production were examined in healthy volunteers before and after experimental intravenous Plasmodium falciparum infection with 150- or 1,800-parasite-infected red blood cells (pRBCs).

Preserved dendritic cell HLA-DR expression and reduced regulatory T cell activation in asymptomatic Plasmodium falciparum and P. vivax infection.

Clinical illness with Plasmodium falciparum or Plasmodium vivax compromises the function of dendritic cells (DC) and expands regulatory T (Treg) cells. Individuals with asymptomatic parasitemia have clinical immunity, restricting parasite expansion and preventing clinical disease. The role of DC and Treg cells during asymptomatic Plasmodium infection is unclear.

Neutrophils with myeloid derived suppressor function deplete arginine and constrain T cell function in septic shock patients.

Introduction: Impaired T cell function in sepsis is associated with poor outcome, but the mechanisms are unclear. In cancer, arginase-expressing myeloid derived suppressor cells (MDSCs) deplete arginine, impair T cell receptor CD3 zeta-chain expression and T cell function and are linked to poor clinical outcome, but their role during acute human infectious disease and in particular sepsis remains unknown. Hypoarginemia is prevalent in sepsis.

Apoptosis and dysfunction of blood dendritic cells in patients with falciparum and vivax malaria.

Malaria causes significant morbidity worldwide and a vaccine is urgently required. Plasmodium infection causes considerable immune dysregulation, and elicitation of vaccine immunity remains challenging. Given the central role of dendritic cells (DCs) in initiating immunity, understanding their biology during malaria will improve vaccination outcomes.