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| Open AccessOsteocytes directly regulate osteolysis via MYD88 signaling in bacterial bone infection
MYD88 mediates the signal of bacterial infection. Here, in the context of periodontal infection, the authors show that the MYD88 pathway in osteocytes plays a dominant role in regulating osteolysis.
- Tetsuya Yoshimoto
- , Mizuho Kittaka
- & Yasuyoshi Ueki
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Article
| Open AccessThe immune synapses reveal aberrant functions of CD8 T cells during chronic HIV infection
HIV infection over time is thought to result in premature aging and aberrant immune responses including the induction of immunological senescence. Here the authors show altered formation of immune synapses by naive CD8+ T cells and dysregulated synapse functioning at late differentiated stages in people living with HIV.
- Nadia Anikeeva
- , Maria Steblyanko
- & Yuri Sykulev
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Article
| Open AccessThe influenza virus PB2 protein evades antiviral innate immunity by inhibiting JAK1/STAT signalling
The PB2 subunit of the RNA polymerase of influenza virus antagonizes interferon signalling. Here, the authors biochemically characterise the molecular interactions that mediate this, and how this impacts viral replication in the context of different influenza subtypes.
- Hui Yang
- , Yurui Dong
- & Xiufan Liu
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Article
| Open AccessSARS-COV-2 antibody responses to AZD1222 vaccination in West Africa
Data on immune response to the SARS-COV-2 AZD1222 vaccine are limited in African populations. Here, the authors show immunogenicity of the AZD1222 vaccine in two independent cohorts from West Africa, including seroprevalence levels prior to vaccine rollout in January 2021.
- Adam Abdullahi
- , David Oladele
- & Ravindra K. Gupta
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Article
| Open AccessDecoding the spatial chromatin organization and dynamic epigenetic landscapes of macrophage cells during differentiation and immune activation
Here the authors delineate the dynamic changes in 3D genome and epigenome of differentiating macrophages and during infection with Mycobacterium tuberculosis. They reveal a role for NF-κB upon infection and identify SNPs in disease-susceptible loci, including rs1873613 that is located in the anchor of a dynamic chromatin loop.
- Da Lin
- , Weize Xu
- & Gang Cao
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Article
| Open AccessSingle cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection
Detailed insight into how the brain responds to Trypanosoma brucei infection is lacking. Here, single cell and spatial transcriptomics are integrated to characterise this response, identifying a unique crosstalk between microglia and plasma cells.
- Juan F. Quintana
- , Praveena Chandrasegaran
- & Annette MacLeod
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Article
| Open AccessCirculating multimeric immune complexes contribute to immunopathology in COVID-19
During viral infections high levels of antibodies can form soluble immune complexes (sICs) with antigen and trigger Fcγ receptors (FcγR) leading to increased immunopathology. Here the authors measure FcγRs activation by sICs and consider how these may lead to excessive immunopathology during severe SARS-CoV-2 infection.
- Jakob Ankerhold
- , Sebastian Giese
- & Valeria Falcone
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Article
| Open AccessThe SARS-CoV-2 Omicron BA.1 spike G446S mutation potentiates antiviral T-cell recognition
Mutations in the spike of SARS-CoV-2 can result in the escape of the neutralising antibody response but may retain susceptibility to the cellular immune response. Here the authors show the G446S mutation in the spike protein of Omicron BA.1 is associated with altered antigen presentation and potentiates activation of specific T cell immunity.
- Chihiro Motozono
- , Mako Toyoda
- & Takamasa Ueno
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Article
| Open AccessExtracellular fibrinogen-binding protein released by intracellular Staphylococcus aureus suppresses host immunity by targeting TRAF3
Staphylococcus aureus secrete numerous effectors to evade or inhibit the host immune response, yet the mechanism underlying the effectors ability to manipulate the signalling pathways of macrophages remain unclear. Authors utilise in vitro and in vivo models to explore the role of extracellular fibrinogen-binding protein (Efb) in immune response modulation and pathogenicity.
- Xiaokai Zhang
- , Tingrong Xiong
- & Quanming Zou
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Article
| Open AccessStreptococcus agalactiae cadD alleviates metal stress and promotes intracellular survival in macrophages and ascending infection during pregnancy
Perinatal infection with Group B Streptococcus (GBS) is associated with preterm birth, neonatal sepsis, and stillbirth. Here, Korir et al. show that gene cadD, encoding a putative metal efflux transporter, is important for metal detoxification, immune evasion and bacterial proliferation in the pregnant host.
- Michelle L. Korir
- , Ryan S. Doster
- & Jennifer A. Gaddy
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Article
| Open AccessIFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses
The effect of IFITM3 on viral pathogenesis is poorly understood. Here, the authors show that IFITM3 restricts cytomegalovirus pathogenesis by reducing Nogo-B-mediated inflammation in response to viral stimuli.
- M. Clement
- , J. L. Forbester
- & I. R. Humphreys
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Article
| Open AccessStructural and functional characterization of NEMO cleavage by SARS-CoV-2 3CLpro
The authors report crystallographic and computational studies that detail how SARS-CoV-2 3CLpro cleaves the host NF-κB Essential Modulator in addition to its canonical viral substrates. The association with the high fitness of SARS-CoV-2 in humans is discussed.
- Mikhail A. Hameedi
- , Erica T. Prates
- & Daniel Jacobson
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Article
| Open AccessLong-term memory CD8+ T cells specific for SARS-CoV-2 in individuals who received the BNT162b2 mRNA vaccine
mRNA vaccines have been shown to prevent SARS-CoV-2 infection and reduce hospitalization and mortality rates. Here, the authors show evidence of long-term memory CD8 + T cells in individuals who received the BNT162b2 SARS-CoV-2 mRNA vaccine.
- Nozomi Kuse
- , Yu Zhang
- & Masafumi Takiguchi
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Article
| Open AccessNeutralization of hepatitis B virus with vaccine-escape mutations by hepatitis B vaccine with large-HBs antigen
The hepatitis B vaccine is recognised as the most effective approach in reducing hepatitis-B-related morbidity; vaccine-escape mutations are however capable of infecting vaccinated individuals. In this work, authors aim to establish a hepatitis B vaccine candidate, which they assess in rhesus macaques in terms of efficacy and safety.
- Ayaka Washizaki
- , Asako Murayama
- & Takanobu Kato
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Article
| Open AccessIntegrated relationship of nasopharyngeal airway host response and microbiome associates with bronchiolitis severity
Bronchiolitis is major cause of infection, morbidity and hospitalisation. Here the authors apply transcriptomic based assessment of the host response, microbiome composition and function, and associate this to bronchiolitis severity.
- Michimasa Fujiogi
- , Yoshihiko Raita
- & Kohei Hasegawa
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Article
| Open AccessPneumolysin boosts the neuroinflammatory response to Streptococcus pneumoniae through enhanced endocytosis
Pneumococcal infection of the cerebrospinal fluid results in bacterial lysis, the release of toxic factors and induction of neuroinflammation. Here, the authors show that the virulence factor pneumolysin enhances the neuroinflammatory response to Streptococcus pneumoniae by the enhancement of endocytosis.
- Sabrina Hupp
- , Christina Förtsch
- & Asparouh I. Iliev
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Article
| Open AccessThe protein arginine methyltransferase PRMT9 attenuates MAVS activation through arginine methylation
The anti-viral protein MAVS forms aggregates as part of the antiviral response and promoting type I IFN responses. Here the authors show that protein arginine methyltransferase 9 (PRMT9) methylates MAVS to keep the protein in a non-aggregated state and propose a regulatory mechanism for MAVS.
- Xuemei Bai
- , Chao Sui
- & Chengjiang Gao
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Article
| Open AccessCircular RNA circTmem241 drives group III innate lymphoid cell differentiation via initiation of Elk3 transcription
Innate lymphoid cells (ILC) have been shown to be involved in a range of inflammatory contexts but how their cellular lineage is regulated is not fully established. Here the authors show a role for circular RNA circTmem241 in the differentiation of ILC3 via initiation of Elk3 transcription.
- Nian Liu
- , Jiacheng He
- & Zusen Fan
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Article
| Open AccessRestructured membrane contacts rewire organelles for human cytomegalovirus infection
Membrane contact sites link organelles to coordinate cell functions. Comparing herpesvirus, influenza, and coronavirus infections, the authors define the virus-driven rewiring of organelle contact sites, uncovering ER-mitochondria encapsulation structures as well as a role for ER contacts in pro-viral peroxisome remodeling.
- Katelyn C. Cook
- , Elene Tsopurashvili
- & Ileana M. Cristea
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Article
| Open AccessMicrobe capture by splenic macrophages triggers sepsis via T cell-death-dependent neutrophil lifespan shortening
Hyperinflammation and immune dysfunction are key drivers of immunopathology in sepsis. Here the authors show microbial exploitation of phagocytic receptors is linked to triggering of sepsis and the immune cell mediated reduction in neutrophil life span.
- Marianna Ioannou
- , Dennis Hoving
- & Venizelos Papayannopoulos
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Article
| Open AccessMaturation and substrate processing topography of the Plasmodium falciparum invasion/egress protease plasmepsin X
Egress of Plasmodium from host erythrocytes is mediated by effector proteins. Aspartic protease plasmepsin X (PM X) regulates the activity for many of these effectors, is essential for replication and is a promising drug target. Here, Mukherjee et al. map the self-cleavage sites of PM X, show that the N-terminal part of its prodomain is required for intracellular trafficking and correlate the maturation and subcellular activity of PM X in microneme, exoneme and rhoptry organelle function.
- Sumit Mukherjee
- , Suong Nguyen
- & Daniel E. Goldberg
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Article
| Open AccessCAF08 adjuvant enables single dose protection against respiratory syncytial virus infection in murine newborns
Respiratory syncytial virus is a major pathogen with burden observed and associated with childhood infection. Here the authors characterise a cationic adjuvant formulation and show single immunisation results in protection in a murine neonate model of respiratory syncytial virus infection.
- Simon D. van Haren
- , Gabriel K. Pedersen
- & Ofer Levy
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Article
| Open AccessGolgi stress induces SIRT2 to counteract Shigella infection via defatty-acylation
Here the authors revealed a role for the protein deacetylase SIRT2 in Golgi stress, particularly induced by bacterial infection. Shigella secrete effector proteins such as IcsB, which transfers fatty acyl groups to modify host proteins to evade host immune surveillance. The upregulated SIRT2 counteracts this function by removing the fatty acyl groups and enhancing the killing of Shigella.
- Miao Wang
- , Yugang Zhang
- & Hening Lin
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Article
| Open AccessPathogen-selective killing by guanylate-binding proteins as a molecular mechanism leading to inflammasome signaling
Guanylate-binding proteins (GBP) have a function in inflammasome formation and pathogen defence. Here the authors show that these GBP proteins are able to kill certain bacteria and promote selective inflammasome activation and that this is mediated by specific GBP protein regions.
- Shouya Feng
- , Daniel Enosi Tuipulotu
- & Si Ming Man
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Article
| Open AccessDetection of neutralizing antibodies against multiple SARS-CoV-2 strains in dried blood spots using cell-free PCR
Neutralizing antibodies are critical for conferring immunity against SARS-CoV-2. Here, Dahn et al. report a PCR assay termed SONIA (Split-Oligonucleotide Neighboring Inhibition Assay) for measuring neutralizing antibodies against multiple SARS-CoV-2 strains in fingerprick dried blood spot samples.
- Kenneth Danh
- , Donna Grace Karp
- & Cheng-ting Tsai
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Article
| Open AccessAge-dependent changes in circulating Tfh cells influence development of functional malaria antibodies in children
Despite being key drivers of protective antibodies against malaria, little is known regarding the host and parasite factors that influence CD4 T-follicular helper cell and antibody development. Authors utilise samples from a study of children living in an area of high malaria transmission in Uganda, to characterize Tfh cells and functional antibodies to multiple parasites stages.
- Jo-Anne Chan
- , Jessica R. Loughland
- & Michelle J. Boyle
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Article
| Open AccessA third vaccination with a single T cell epitope confers protection in a murine model of SARS-CoV-2 infection
Vaccination regimens and the number of doses required for optimal immunity and protection are critical factors in the translation of vaccines. Here the authors show administration of a three dose protocol of a single T cell epitope to the SARS-CoV-2 spike protein induces a robust CD8+ T cell response and confers protection in a lethal murine challenge model of infection.
- Iris N. Pardieck
- , Tetje C. van der Sluis
- & Ramon Arens
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Article
| Open AccessUpper airway gene expression shows a more robust adaptive immune response to SARS-CoV-2 in children
The difference between children and adults in response to SARS-CoV-2 infection is not clearly established. Here the authors use gene expression analysis of nasopharyngeal samples from children and adults and show a higher level of immune response in children compared to adults, including of B and T cell activation.
- Eran Mick
- , Alexandra Tsitsiklis
- & Charles R. Langelier
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Article
| Open AccessViral coinfection promotes tuberculosis immunopathogenesis by type I IFN signaling-dependent impediment of Th1 cell pulmonary influx
Viral coinfection alongside mycobacterium tuberculosis (Mtb) infection may lead to immune complications or interference with immune responses. Here the authors show that in mice infected with Mtb and LCMV virus the specific TH1 response to MTb is reduced through a type I IFN response to the infecting virus.
- Tae Gun Kang
- , Kee Woong Kwon
- & Sung Jae Shin
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Article
| Open AccessGenomic dissection of Klebsiella pneumoniae infections in hospital patients reveals insights into an opportunistic pathogen
Klebsiella pneumoniae is an opportunistic pathogen of increasing public health concern due to the prevalence of antimicrobial resistance. Here, the authors provide insight into the resistance profiles, bacterial genome features and virulence genes, in a year-long prospective study of K. pneumoniae clinical isolates.
- Claire L. Gorrie
- , Mirjana Mirčeta
- & Kathryn E. Holt
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Article
| Open AccessImmunoprofiling reveals cell subsets associated with the trajectory of cytomegalovirus reactivation post stem cell transplantation
Human cytomegalovirus is a major cause of morbidity and mortality in transplant patients and multiple immune cells types are critical during infection and reactivation. Here the authors assess the immune cell compartments of haematopoietic stem cell recipients in the early period post transplantation and identify key features of effector memory CD4+ T cells and mucosal associated invariant T cells in this context.
- Lauren Stern
- , Helen M. McGuire
- & Barry Slobedman
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Article
| Open AccessCinA mediates multidrug tolerance in Mycobacterium tuberculosis
Drug tolerance complicates the treatment of tuberculosis. Here, Kreutzfeldt et al. show that the protein CinA mediates drug tolerance in Mycobacterium tuberculosis by cleaving NAD-drug adducts, suggesting CinA as a potential target to shorten tuberculosis treatment by potentiating the efficacy of currently used antibiotics.
- Kaj M. Kreutzfeldt
- , Robert S. Jansen
- & Sabine Ehrt
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Article
| Open AccessDifferential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model
Model systems to study SARS-CoV-2 infection are required to better understand the immune response. Here the authors use a lung and macrophage co-culture system by differentiation of human pluripotent stem cells to better understand the phenotype and gene expression changes in host lung cells and macrophages after SARS-CoV-2 infection in vitro.
- Qizhou Lian
- , Kui Zhang
- & Huanhuan Joyce Chen
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Article
| Open AccessLung type II alveolar epithelial cells collaborate with CCR2+ inflammatory monocytes in host defense against poxvirus infection
Smallpox is a highly contagious respiratory pathogen associated with a high mortality rate. Here the authors utilize a mouse model of intranasal vaccinia virus infection and show a C7 gene encoded virulence factor attenuates type I IFN release by lung type II alveolar epithelial cells and reduces lung inflammatory monocyte responses.
- Ning Yang
- , Joseph M. Luna
- & Liang Deng
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Article
| Open AccessInhibition of lung microbiota-derived proapoptotic peptides ameliorates acute exacerbation of pulmonary fibrosis
Here, the authors show that treatment with a monoclonal neutralizing antibody against the lung microbiota-derived proapoptotic peptide corisin ameliorates acute exacerbation of pulmonary fibrosis and severity of endotoxin-induced acute lung injury in mice.
- Corina N. D’Alessandro-Gabazza
- , Taro Yasuma
- & Esteban C. Gabazza
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Article
| Open AccessDivergent trajectories of antiviral memory after SARS-CoV-2 infection
The engagement of immunological memory is a key component to the protective anti-SARS-CoV-2 B and T cell responses. Here the authors assess the B and T cells of a cohort of UK healthcare workers in response to infection and longitudinally track the compartment showing distinct trajectories following early priming.
- Adriana Tomic
- , Donal T. Skelly
- & Susanna J. Dunachie
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Article
| Open AccessProtective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection
Infection with SARS-COV-2 can result in self-limited upper airway infection or progress to a more systemic inflammatory condition including pneumonic COVID-19. Here the authors utilise a multi-omics approach to interrogate the immune response of patients with self-limiting upper respiratory SARS-CoV-2 infection and reveal a temporal immune trajectory they associate with viral containment and restriction from pneumonic progressive disease.
- Kami Pekayvaz
- , Alexander Leunig
- & Leo Nicolai
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Article
| Open AccessIdentification and establishment of type IV interferon and the characterization of interferon-υ including its class II cytokine receptors IFN-υR1 and IL-10R2
Interferons are critical soluble components of the inflammatory process and are composed of three types with associated receptor complexes. Here the authors identify and characterise the type IV interferon, IFN-υ, and identify its associated receptors, denote functionality during in vivo infection and ascertain its genomic localisation.
- Shan Nan Chen
- , Zhen Gan
- & Pin Nie
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Article
| Open AccessRough and smooth variants of Mycobacterium abscessus are differentially controlled by host immunity during chronic infection of adult zebrafish
The pathogen Mycobacterium abscessus can switch from a smooth colony form (S) into a highly inflammatory, rough colony form (R) during infection. Here, Kam et al. use an adult zebrafish model of M. abscessus chronic infection to illustrate differences in the immunopathogenesis induced by R and S variants.
- Julia Y. Kam
- , Elinor Hortle
- & Stefan H. Oehlers
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Article
| Open AccessPrognostic tools and candidate drugs based on plasma proteomics of patients with severe COVID-19 complications
Prognostic markers for patients with COVID-19 are of critical importance in determining the course of SARS-CoV-2 infection and patient handling. Here the authors determine and apply a prognostic proteomic panel for risk and drug prediction in the management of SARS-CoV-2 infected patients.
- Maryam A. Y. Al-Nesf
- , Houari B. Abdesselem
- & Fares Al-Ejeh
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Article
| Open AccessEarly alveolar macrophage response and IL-1R-dependent T cell priming determine transmissibility of Mycobacterium tuberculosis strains
Halting tuberculosis transmission is crucial to TB elimination. Here the authors implicate IL-1R dependent T cell priming as the underlying mechanism determining variability in transmission of Mycobacterium tuberculosis strains.
- Arianne Lovey
- , Sheetal Verma
- & Padmini Salgame
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Article
| Open AccessIL-22 initiates an IL-18-dependent epithelial response circuit to enforce intestinal host defence
IL-22 induces IL-18 expression by intestinal epithelial cells. Authors show here that IL-18 is a key barrier maintenance factor during adherent-invasive E. coli invasion, inducing expression of anti-microbial genes in Paneth cells via Stat3, prompting IFNγ expression in T cells and triggering intestinal Lgr5+ stem cell expansion via Tcf4.
- Hung-Yu Chiang
- , Hsueh-Han Lu
- & Jr-Wen Shui
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Article
| Open AccessTranslocated Legionella pneumophila small RNAs mimic eukaryotic microRNAs targeting the host immune response
Legionella pneumophila expresses a range of bacterial determinants that mimic eukaryotic functions. Here the authors show small RNAs of L.pneumophila mimic eukaryotic microRNA and modulate the host response to infection.
- Tobias Sahr
- , Pedro Escoll
- & Carmen Buchrieser
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Article
| Open AccessImmunoglobulin signature predicts risk of post-acute COVID-19 syndrome
Studying a prospective cohort, the authors develop and validate a predictive score for post-acute COVID-19 syndrome, also known as long-COVID. This score relies on an immunoglobulin signature and is independent of timepoint of blood sampling.
- Carlo Cervia
- , Yves Zurbuchen
- & Onur Boyman
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Article
| Open AccessAdenosine receptor 2a agonists target mouse CD11c+T-bet+ B cells in infection and autoimmunity
CD11c+T-bet+ B cells have been linked with different autoimmune diseases, but targeting these cells has been challenging. Here the authors use an adenosine 2A receptor agonist to deplete these B cells and to inhibit or reverse autoimmune symptoms and pathology in mice.
- Russell C. Levack
- , Krista L. Newell
- & Gary M. Winslow
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Article
| Open AccessOxylipin metabolism is controlled by mitochondrial β-oxidation during bacterial inflammation
Oxylipins are lipid mediators generated during infection for regulating inflammatory responses, but how they are removed is not completely clear. Here the authors show that cellular oxylipin removal is linked to mitochondria β-oxidation by CPT1, a mitochondria lipid importer protein, to serve as a metabolic checkpoint for oxylipin homeostasis and inflammation.
- Mariya Misheva
- , Konstantinos Kotzamanis
- & Valerie B. O’Donnell
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Article
| Open AccessThe transcription factor ZIP-1 promotes resistance to intracellular infection in Caenorhabditis elegans
Intestinal immune responses to intracellular infection of Caenorhabditis elegans and other Invertebrate hosts are not well understood. Here the authors show a key role for the transcription factor ZIP-1 during intestinal intracellular infection.
- Vladimir Lažetić
- , Fengting Wu
- & Emily R. Troemel
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Article
| Open AccessDelayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2
The innate immune response in epithelial cells after SARS-CoV-2 infection is not fully understood. Here the authors use human air-liquid interface culture and show single cell transcription changes and delayed type I Interferon responses after SARS-CoV-2 infection compared with other respiratory viruses.
- Catherine F. Hatton
- , Rachel A. Botting
- & Christopher J. A. Duncan
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Review Article
| Open AccessEmerging technologies and infection models in cellular microbiology
Cellular microbiology is a field that combines the study of infection and cell biology. In this review, we highlight emerging technologies and infection models that recently transformed our understanding of the infected cell and may inspire future medicine.
- Ana Teresa López-Jiménez
- & Serge Mostowy