Inflammation

  • Article
    | Open Access

    Sepsis caused by the release of inflammatory mediators into the blood is a life threatening disease. Here, the authors report on the development of hydrogel nanoparticles for the capture and neutralisation of histones, major inflammatory mediators, and demonstrate sepsis treatment in a murine model.

    • Hiroyuki Koide
    • , Anna Okishima
    •  & Kenneth J. Shea
  • Article
    | Open Access

    Myeloid cells are implicated in the innate immune and inflammatory response during infection with Chlamydia trachomatis. Here the authors show the evasion of the neutrophil response to infection and concomitant induction of sterile immunity via the purinergic P2X7 receptor.

    • Chunfu Yang
    • , Lei Lei
    •  & Harlan D. Caldwell
  • Article
    | Open Access

    Here, the authors perform transcriptional profiling on tracheal aspirates of adults requiring mechanical ventilation for SARS-CoV2-induced acute respiratory distress syndrome (ARDS) and identify a dysregulated host response predicted to predicted to be potentially modulated by dexamethasone.

    • Aartik Sarma
    • , Stephanie A. Christenson
    •  & Charles R. Langelier
  • Article
    | Open Access

    Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

    • Noam D. Beckmann
    • , Phillip H. Comella
    •  & Alexander W. Charney
  • Article
    | Open Access

    Post-translational modifications are important regulators of NLRP3 inflammasome activity. Here the authors show that the E3 ligase TRIM28 can SUMOylate NLRP3, thereby limiting its proteasomal degradation and increasing NLRP3 inflammasome activity.

    • Ying Qin
    • , Qi Li
    •  & Wei Zhao
  • Article
    | Open Access

    During wound healing and infection in the skin there is a hypoxic environment involving HIF-1α and NK cells. Here the authors show that NK cells through HIF-1α provide a cross-regulatory balance to provide an adequate antimicrobial defence that can inhibit subsequent wound healing.

    • Michal Sobecki
    • , Ewelina Krzywinska
    •  & Christian Stockmann
  • Article
    | Open Access

    SARS-CoV-2 infection has been shown to drive NLRP3 inflammasome activation and thereby cytokine storm, but how it does so is unclear. Here the authors show that the viral N protein can bind to NLRP3, resulting in enhanced interaction with ASC and thereby with the NLRP3 inflammasome.

    • Pan Pan
    • , Miaomiao Shen
    •  & Jianguo Wu
  • Article
    | Open Access

    SARS-CoV-2 infection of expecting mothers has been reported. Here the authors profile the peripheral blood from 14 pregnant women with asymptomatic or mild SARS-CoV-2 infection to find grossly normal immune cell composition but heterogenous induction of pro-inflammatory cytokines, thereby implicating possible therapeutic targets for virus-induced damages during pregnancy.

    • Sara De Biasi
    • , Domenico Lo Tartaro
    •  & Andrea Cossarizza
  • Article
    | Open Access

    The serine/threonine kinase WNK1 is an inhibitor of chloride efflux. Here the authors show that this inhibition is a means of negatively regulating the activation of the NLRP3 inflammasome in macrophages, leading to reduced inflammatory responses.

    • Lindsey Mayes-Hopfinger
    • , Aura Enache
    •  & Emad S. Alnemri
  • Article
    | Open Access

    3-hydroxy-L-kynurenamine (3-HKA) is a metabolite deriving from a lateral pathway of tryptophan catabolism. Here the authors identify 3-HKA as a biogenic amine and show it has anti-inflammatory properties that can protect mice against psoriasis and nephrotoxic nephritis.

    • Cristina C. Clement
    • , Angelo D’Alessandro
    •  & Laura Santambrogio
  • Article
    | Open Access

    Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 and poor outcomes. Here the authors compare the transcriptomes of single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in these patients.

    • Linh T. Bui
    • , Nichelle I. Winters
    •  & Laure Emmanuelle Zaragosi
  • Article
    | Open Access

    Iron is essential during pregnancy for embryo and placental development and maternal health. However, in this study using mouse models, the authors demonstrate that excess maternal iron causes adverse embryo outcomes in pregnancies with underlying systemic inflammation.

    • Allison L. Fisher
    • , Veena Sangkhae
    •  & Elizabeta Nemeth
  • Article
    | Open Access

    Previous studies have shown that the CD40L-CD40 signaling axis plays a role in atherosclerosis. Here the authors investigate the cell-specific functions of the most relevant CD40L-expressing cell types in atherosclerosis. Deficiency of T cell-derived CD40L reduces and stabilizes plaques through impaired Th1 polarization while platelet-derived CD40L ameliorates atherothrombosis.

    • Michael Lacy
    • , Christina Bürger
    •  & Esther Lutgens
  • Article
    | Open Access

    Bacterial or viral infection can lead to lethal systemic inflammation and thrombosis. Here, the authors show that inhibiting integrin outside-in signaling in leukocytes and platelets alleviates inflammation/clotting and improved survival in septic mice.

    • Ni Cheng
    • , Yaping Zhang
    •  & Xiaoping Du
  • Article
    | Open Access

    Body cavity macrophages reside on the serous surfaces of organs and believed to participate in organ repair following injury. Here the authors show with a fate-mapping reporter system that these cells, although accumulate at the surfaces of injured liver or lung, don’t penetrate deeply into the tissue.

    • Hengwei Jin
    • , Kuo Liu
    •  & Bin Zhou
  • Article
    | Open Access

    Endothelial tissues must have intact barrier function, but this may be disrupted during inflammation. Here, the authors show that the mitochondrial protein Mitofusin-2 stabilizes cell–cell adherens junctions in endothelial cells during homeostasis and binds the transcriptional activator β-catenin upon inflammatory stimulation.

    • Young-Mee Kim
    • , Sarah Krantz
    •  & Jalees Rehman
  • Article
    | Open Access

    Asthma is caused by hyperreactivity to benign antigens, with humoral immunity orchestrated by interleukin-4 (IL-4) and IL-13 being the key etiological factor. Here the authors show, in humanized mouse models, that dual vaccination against IL-4 and IL-13 induces their durable suppression ameliorate experimental asthma, and to hint clinical translation.

    • Eva Conde
    • , Romain Bertrand
    •  & Laurent L. Reber
  • Article
    | Open Access

    Despite being prevalent yet well studied, ulcerative colitis still has poorly characterized pathophysiology. Here the authors use mouse colitis models to find that type I and III interferon (IFN) both contribute to ameliorating the disease, with IFN signaling in either the epithelial or hematopoietic compartment sufficient for this protective effect.

    • Constance McElrath
    • , Vanessa Espinosa
    •  & Sergei V. Kotenko
  • Article
    | Open Access

    Here, the authors combine 16 S rRNA sequencing, culture and bioinformatics to profile the microbiome in 234 serial bronchoalveolar lavage samples from 64 lung transplant recipients collected over 49-months and identify distinct compositional states, termed pneumotypes, linked to current health status, and establish a collection of primary lung bacterial isolates, LuMiCol.

    • Sudip Das
    • , Eric Bernasconi
    •  & Laurent P. Nicod
  • Article
    | Open Access

    Mito-SEPs are small peptides that can modulate oxidative metabolism in mitochondria. Here the authors show that C15ORF48 encodes a mito-SEP, MOCCI, capable of altering mitochondria respiration to suppress inflammation, while C15ORF48 3’ untranslated region also contains a miRNA, miR-147b, that synergizes with MOCCI to modulate host anti-viral responses.

    • Cheryl Q. E. Lee
    • , Baptiste Kerouanton
    •  & Lena Ho
  • Article
    | Open Access

    Lipocalin 2 (LCN2) has been recently identified as an endogenous regulator of appetite. Here, using pancreatic cancer as a model of cachexia, the authors demonstrate that LCN2 is a critical mediator of cancer-associated anorexia and may be therapeutically targeted to improve patient outcomes.

    • Brennan Olson
    • , Xinxia Zhu
    •  & Daniel L. Marks
  • Article
    | Open Access

    Mitochondrial content in extracellular vesicles (EVs) can enhance inflammation, although its role in noninflammatory conditions is unclear. Here, the authors show that mitochondria-derived vesicles target material to EVs, whereas Parkin directs damaged mitochondrial content to lysosomes, providing insight into mitochondria-driven immune responses.

    • Kiran Todkar
    • , Lilia Chikhi
    •  & Marc Germain
  • Article
    | Open Access

    The peritoneal cavity is a complicated myeloid niche containing a mixed population of resident macrophages and infiltrating cells that are responsive to inflammatory cues. Here the authors trace the fate of these infiltrating macrophages, their conversion to resident cells and how this is altered by the local inflammatory state over time.

    • P. A. Louwe
    • , L. Badiola Gomez
    •  & S. J. Jenkins
  • Article
    | Open Access

    It is unknown whether capsulized fecal microbiota transplantation (FMT) can modify the microbiota of people with HIV. Here, the authors report the results of a pilot double-blind study, where 30 HIV-infected subjects on ART were randomized to either weekly oral FMT capsules or placebo for 8 weeks, and show that transplanted microbiota successfully engrafts and is able to attenuate HIV-associated dysbiosis.

    • Sergio Serrano-Villar
    • , Alba Talavera-Rodríguez
    •  & Santiago Moreno
  • Article
    | Open Access

    Inflammatory bowel diseases are heterogeneous, and little is known about how underlying genetic variation can affect their development. Here, the authors report that intestinal inflammation modulates the effect of host genetics on the gut mucosal expression of 190 genes in the context of inflammatory bowel diseases.

    • Shixian Hu
    • , Werna T. Uniken Venema
    •  & Rinse K. Weersma
  • Article
    | Open Access

    Macrophages may polarize into different states with distinct regulatory functions for inflammation. Here the authors perform high-throughput in vitro screening of a library of ~4000 compounds to identify those with specific effects on human macrophage polarization, while RNAseq helps uncover the targets and pathways mediating these effects.

    • Guangan Hu
    • , Yang Su
    •  & Jianzhu Chen
  • Article
    | Open Access

    The tumor microenvironment is composed of many cell types that crosstalk to modulate local immunity. Here the authors show that Amyloid β proteins from cancer-associated fibroblasts (CAF) induce neutrophil extracellular trap (NET) production by neutrophils, while NET feeds back to activate CAF, thereby implicating Amyloid β as a potential therapy target.

    • Hafsa Munir
    • , James O. Jones
    •  & Jacqueline D. Shields
  • Article
    | Open Access

    Genetic elements that control inflammatory gene expression are not fully elucidated. Here the authors conduct a multi-species analysis of chromatin landscape and NF-κB binding in response to the proinflammatory cytokine TNFα, finding that conserved NF-κB bound regions are linked to enhancer activity and disease.

    • Azad Alizada
    • , Nadiya Khyzha
    •  & Michael D. Wilson
  • Article
    | Open Access

    Trafficking of IgA/commensal complex in the gut has been implicated in inflammatory bowel diseases such as Crohn’s disease, but molecular insights are still lacking. Here the authors show, using mouse model or human cells, that NOD2 mutation increases IgA transport, potentially by altering gut microfold cells from the gut, to impact gut inflammation.

    • Nicolas Rochereau
    • , Xavier Roblin
    •  & Stéphane Paul
  • Article
    | Open Access

    NLRP1 and CARD8 are two recently described sensor proteins for the human inflammasome complex. Here, the authors present the cryo-EM CARD filament structures of the NLRP1 and CARD8 activating domains, which reveal how NLRP1 and CARD8 discriminate between ASC and pro-caspase-1. They further propose a two-step model for NLRP1 activation.

    • Qin Gong
    • , Kim Robinson
    •  & Bin Wu
  • Article
    | Open Access

    Control of mosquito populations using pesticides is important for malaria elimination, but effects of pesticides on humans aren’t well understood. Here, Prahl et al. show in a cohort of pregnant Ugandan women and their infants that household spraying with bendiocarb affects the fetal immune system and response to vaccination in infancy.

    • Mary Prahl
    • , Pamela Odorizzi
    •  & Margaret E. Feeney
  • Article
    | Open Access

    Unlike RORα, which has been thought to be somewhat redundant, RORγt has been well characterized in its function and contribution to the development of Th17 cells. Here the authors show that RORα is important in Th17 differentiation and that RORα deletion or a small molecule inhibitor of RORα can reduce disease in EAE and colitis mouse models.

    • Ran Wang
    • , Sean Campbell
    •  & Laura A. Solt
  • Article
    | Open Access

    Mannose is present at trace levels in blood and regulates cancer growth. Here the authors show that supraphysiological levels of mannose can also regulate macrophages, limiting their production of IL-1β and increasing resistance of mice to LPS-induced endotoxemia and DSS-induced colitis.

    • Simone Torretta
    • , Alessandra Scagliola
    •  & Simone Cardaci
  • Article
    | Open Access

    The development of specific anti-cytokine/chemokine therapeutic strategies for atherosclerotic disease is challenging. Here, the authors have designed a peptide-based ectodomain mimic of the chemokine receptor CXCR4 that selectively targets MIF but not CXCL12 and blocks experimental atherosclerosis in vivo.

    • Christos Kontos
    • , Omar El Bounkari
    •  & Jürgen Bernhagen
  • Article
    | Open Access

    The cytokine like protein FAM3D (Fam3D in mice) is highly expressed in the digestive tract with unknown role in colon pathophysiology. Here, by using gene deficient mice, the authors show that Fam3D is critically involved in colon homeostasis, host defense against colitis-associated carcinogenesis, and the balance of microbiota.

    • Weiwei Liang
    • , Xinjian Peng
    •  & Ying Wang
  • Article
    | Open Access

    Chronic obstructive pulmonary disease (COPD) is a progressing disease, with lung but not gut microbiota implicated in its etiology. Here the authors compare the stool from patients with COPD and healthy controls to find specific gut bacteria and metabolites associated with active disease, thereby hinting at a potential role for the gut microbiome in COPD.

    • Kate L. Bowerman
    • , Saima Firdous Rehman
    •  & Philip M. Hansbro
  • Article
    | Open Access

    Inflammation contributes to the development of metabolic disease through incompletely understood mechanisms. Here the authors report that deletion of the transcription factor KLF2 in myeloid cells leads to increased feeding and weight gain in mice with concomitant peripheral and central tissue inflammation, while overexpression protects against diet-induced metabolic disease.

    • David R. Sweet
    • , Neelakantan T. Vasudevan
    •  & Mukesh K. Jain
  • Article
    | Open Access

    Breakdown of vascular barriers is a major complication of inflammatory diseases. However, the mechanisms underlying platelet recruitment to inflammatory micro-environments remains unclear. Here, the authors identify haptotaxis as a key effector function of immune-responsive platelets

    • Leo Nicolai
    • , Karin Schiefelbein
    •  & Florian Gaertner
  • Article
    | Open Access

    GM-CSF is involved in control over M. tuberculosis infection. Here the authors show that GM-CSF reduces type 1 interferon driven neutrophil recruitment, NETosis and bacterial growth in the lungs of infected mice, and provide evidence that this NETosis occurs in infected humans who are not responsive to antibiotic therapy.

    • Lúcia Moreira-Teixeira
    • , Philippa J. Stimpson
    •  & Anne O’Garra
  • Article
    | Open Access

    Cardiac dysfunction is a major complication that precedes death after scorpion envenomation. Here, authors show that heart failure and mortality are caused by excessive acetylcholine release, which requires IL-1R-dependent PGE2 production. Dexamethasone treatment effectively inhibits cardiac dysfunction and mortality.

    • Mouzarllem B. Reis
    • , Fernanda L. Rodrigues
    •  & Lúcia H. Faccioli
  • Article
    | Open Access

    Inflammasome activation may contribute to type 2 diabetes, but whether targeting inflammasome is beneficial is unclear. Here the authors show that repurposing nucleoside reverse transcriptase inhibitors for inhibiting inflammasome activation is associated with reduced diabetes development in people and improves insulin sensitivity in experimental settings.

    • Jayakrishna Ambati
    • , Joseph Magagnoli
    •  & Bradley D. Gelfand
  • Article
    | Open Access

    Culture-based diagnostic methods for microorganism detection are time-consuming but still the gold standard for conditions such as sepsis. Here the authors present an amplification and purification-free method to detect microorganisms in bodily fluids with high sensitivity: Single MOLecule Tethering (SMOLT).

    • Wen-Chih Cheng
    • , Troy Horn
    •  & Alfredo Celedon
  • Article
    | Open Access

    Psoriatic arthritis (PsA) commonly affects patients with skin psoriasis, but its pathogenesis is still unclear. Here the authors use two types of single-cells data, mass cytometry and RNA sequencing, to describe the expansion and diversity of synovial, but not peripheral blood, CD8 T cells from PsA patients to provide a molecular immune landscape for PsA.

    • Frank Penkava
    • , Martin Del Castillo Velasco-Herrera
    •  & M. Hussein Al-Mossawi
  • Article
    | Open Access

    Group 2 innate lymphoid cells (ILC2s) are immune cells present in adipose tissue that contribute to metabolic homeostasis. Here the authors show that Death Receptor 3 (DR3) engagement on ILC2s ameliorates glucose tolerance, protects against insulin-resistance onset and reverses established insulin-resistance.

    • Pedram Shafiei-Jahani
    • , Benjamin P. Hurrell
    •  & Omid Akbari