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| Open AccessFrancisella tularensis induces Th1 like MAIT cells conferring protection against systemic and local infection
Mucosal-Associated Invariant T (MAIT) cells are associated with established functions during bacterial infection. Here the authors show inoculation with Francisella tularensis results in induction of MAIT cells associated with prototypic Th1 immunity and confer protection to systemic and local infection.
- Zhe Zhao
- , Huimeng Wang
- & Zhenjun Chen
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Article
| Open AccessTwelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan
COVID-19 pandemic is a global health risk, but our understanding on the induced durable immunity remains scarce. Here the authors assess antibody responses in 869 convalescent COVID-19 patients to find that specific antibody titers reduce with time, and the RBD-IgG positive rate exceed 70% at 12 month post diagnosis, with male and older patients showing stronger responses.
- Cesheng Li
- , Ding Yu
- & Xiaoming Yang
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Article
| Open AccessSARS-CoV-2-specific T cell memory is sustained in COVID-19 convalescent patients for 10 months with successful development of stem cell-like memory T cells
T cells are instrumental to protective immune responses against SARS-CoV-2, the pathogen responsible for the COVID-19 pandemic. Here the authors show that, in convalescent COVID-19 patients, memory T cell responses are detectable up to 317 days post-symptom onset, in which the presence of stem cell-like memory T cells further hints long-lasting immunity.
- Jae Hyung Jung
- , Min-Seok Rha
- & Eui-Cheol Shin
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Article
| Open AccessImmunological imprinting of the antibody response in COVID-19 patients
In addition to SARS-CoV-2, other coronaviruses also infect human, but whether consecutive infections cross-modulate the induced immune response is still unclear. Here the authors show that SARS-CoV-2 infection boosts pre-existing responses to other coronaviruses, yet such back-boosting hampers the induction of specific antibodies against SARS-CoV-2.
- Teresa Aydillo
- , Alexander Rombauts
- & Adolfo García-Sastre
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Article
| Open AccessClinical and molecular characteristics of COVID-19 patients with persistent SARS-CoV-2 infection
Some patients with COVID-19 fail to clear the viral infection quickly, yet our understanding for the underlying immune characteristics is still lacking. Here the authors use single-cell RNA sequencing and other data form such patients to show that persistent infection is associated with immune suppression and reduced expression of ribosomal protein genes.
- Bin Yang
- , Junpeng Fan
- & Chaoyang Sun
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Article
| Open AccessNociceptive sensory neurons promote CD8 T cell responses to HSV-1 infection
Herpes simplex virus 1 (HSV-1) is a neurotropic virus that often cause pain via the induction of ulcer or blisters. Here the authors show, in mouse models of HSV-1 infection, that the pain-perceiving nociceptor Nav1.8+ neurons contribute to regulating both innate and adaptive immune responses against HSV-1, thereby offering a potential target for therapy.
- Jessica Filtjens
- , Anais Roger
- & Sophie Ugolini
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Article
| Open AccessNeutralizing antibody responses to SARS-CoV-2 in symptomatic COVID-19 is persistent and critical for survival
Antibody responses are critical for protection from developing severe COVID-19 following SARS-CoV-2 infection. Here the authors show that antibody responses against SARS-CoV-2 spike protein correlate with neutralizing capacity and protection, are not affected by heterologous boosting of influenza or common cold immunity, and can last up to 8 months.
- Stefania Dispinseri
- , Massimiliano Secchi
- & Gabriella Scarlatti
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Article
| Open AccessAn infection-induced RhoB-Beclin 1-Hsp90 complex enhances clearance of uropathogenic Escherichia coli
Bacterial invasion can lead to multiple host cell responses. Here, the authors show that in a model of uropathogenic E. coli, RhoB is upregulated and induces autophagosome formation in a complex with Beclin1 and Hsp90, promoting bacterial clearance.
- Chunhui Miao
- , Mingyu Yu
- & Quan Wang
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Article
| Open AccessIFN-γ-dependent NK cell activation is essential to metastasis suppression by engineered Salmonella
Cancer metastasis is one of the major causes of cancer related deaths and there is an urgent need to find more clinically effective metastasis targeting agents. Here, the authors show that Salmonella YB1 inhibits metastasis in multiple mouse models of cancer through a mechanism dependent on IFN-γ and NK cells.
- Qiubin Lin
- , Li Rong
- & Jian-Dong Huang
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Article
| Open AccessTREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation
Mycobacterial cell wall lipids can drive immunoevasion, but underlying mechanisms are incompletely understood. Here the authors show TREM2 is a pattern recognition receptor that binds non-glycosylated mycolic acid-containing lipids and inhibits Mincle-induced anti-mycobacterial macrophage responses.
- Ei’ichi Iizasa
- , Yasushi Chuma
- & Hiromitsu Hara
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Article
| Open AccessMonocyte progenitors give rise to multinucleated giant cells
Multinucleated giant cells characterize granuloma formation in mycobacterial infections. Here the authors identify monocyte precursors with distinct immunological and metabolic properties as a source of the granuloma multinucleated giant cell compartment.
- Anne Kathrin Lösslein
- , Florens Lohrmann
- & Philipp Henneke
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Article
| Open AccessSARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself
Our understanding on the humoral immunity induced by SARS-CoV-2 is still lacking. Here the authors analyze B cell responses at the single cell level to find that, in severe COVID-19 patients, plasmablasts shift from IFN to TGFβ instruction to produce IgA antibodies that are not specific to dominant SARS-CoV-2 antigens.
- Marta Ferreira-Gomes
- , Andrey Kruglov
- & Mir-Farzin Mashreghi
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Article
| Open AccessActivation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice
GPR37 is expressed in macrophages, and has been implicated in resolution of inflammatory pain. Here the authors show that GPR37 can modulate sepsis in several animal models.
- Sangsu Bang
- , Christopher R. Donnelly
- & Ru-Rong Ji
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Article
| Open AccessN6-methyladenosine RNA modification suppresses antiviral innate sensing pathways via reshaping double-stranded RNA
N6-methyladenosine (m6A) RNA modification regulates RNA metabolism, and has been implicated in immune regulation. Here, the authors show that the m6A methyltransferase, METTL3, translocates into the cytoplasm to increase viral RNA m6A modification, decreases viral ds RNA content, and thereby dampens the RIG/MDA5-induced anti-viral immunity.
- Weinan Qiu
- , Qingyang Zhang
- & Pengyuan Yang
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Article
| Open AccessLasting antibody and T cell responses to SARS-CoV-2 in COVID-19 patients three months after infection
Understanding if lasting immune responses can be induced by SARS-CoV-2 infection is important for controlling the COVID-19 pandemic. Here, the authors show, in a cohort of 25 patients, that IgG and T cell responses, as well as neutralising antibody, are still detectable against various SARS-CoV-2 proteins 3 months post-symptom onset, while IgM levels largely wane at this time.
- Xiao-Lin Jiang
- , Guo-Lin Wang
- & Mai-Juan Ma
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Article
| Open AccessA multiplex chemiluminescent immunoassay for serological profiling of COVID-19-positive symptomatic and asymptomatic patients
Antibody responses to SARS-CoV-2 may be important biomarkers for assessing the risk for viral transmission. Here the authors present serological antibody profiling results of COVID-19 patients using a new multiplex assay to show distinct kinetics and dynamics of IgG, IgM and IgA responses in patients with different disease severity.
- Allison N. Grossberg
- , Lilia A. Koza
- & Daniel A. Linseman
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Article
| Open AccessHuman antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis
Antibody responses against Mycobacteria infection have been reported, but whether and how they impact anti-bacteria immunity in the host is unclear. Here the authors characterize human anti-Mycobacteria antibodies to find them targeting a Mycobacteria transporter protein, PstS1, show distinct interaction modes in crystal structure, and mediate protection in vitro.
- Avia Watson
- , Hao Li
- & Natalia T. Freund
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Article
| Open AccessDisease-associated gut microbiome and metabolome changes in patients with chronic obstructive pulmonary disease
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
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Article
| Open AccessDermal IRF4+ dendritic cells and monocytes license CD4+ T helper cells to distinct cytokine profiles
Antigen presenting cells induce CD4+ T helper (Th) differentiation upon pathogen encounters. Here the authors use fluorescently-labeled bacteria, helminth and fungi to track and describe the functions of IRF4+ migratory type 2 dendritic cells and monocytes in the specific induction of Th1, Th2 or Th17 responses following skin inoculation.
- Kerry L. Hilligan
- , Shiau-Choot Tang
- & Franca Ronchese
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Article
| Open AccessBroadly neutralizing plasma antibodies effective against autologous circulating viruses in infants with multivariant HIV-1 infection
Some infants develop broadly neutralizing antibodies (bnAbs) to HIV in a shorter time frame than adults, but the reasons aren’t well understood. Here, the authors study a cohort of 51 HIV-1 clade C perinatally infected infants of Indian origin and find that multivariant infection is associated with bnAbs in elite neutralizers.
- Nitesh Mishra
- , Shaifali Sharma
- & Kalpana Luthra
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Article
| Open AccessInherited salt-losing tubulopathies are associated with immunodeficiency due to impaired IL-17 responses
Salt levels in culture affect the polarisation of Th17 cells, which normally protect the host from fungal and bacterial infections. Here, the authors study patients with salt-losing tubulopathies (SLT) to find that, while Th17 immunity is dampened in SLT patients, their Th17-inducing signaling pathways are intact and can be reinvigorated by exogenous salt.
- Rhys D. R. Evans
- , Marilina Antonelou
- & Alan D. Salama
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Article
| Open AccessSingle-cell analysis of two severe COVID-19 patients reveals a monocyte-associated and tocilizumab-responding cytokine storm
Tocilizumab has been used to treat the excessive inflammatory responses in COVID-19 patients. Here, the authors use single-cell RNA sequencing results from two severe COIVD-19 patients to provide high-dimensional immune profiling data, and to implicate potential cellular and molecular insights for the therapeutic effects of tocilizumab.
- Chuang Guo
- , Bin Li
- & Kun Qu
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Article
| Open AccessActivation and evasion of type I interferon responses by SARS-CoV-2
The pandemic of SARS-CoV-2 post a significant threat to public health. Here the authors show, by screening 23 viral proteins, that both structural and non-structural SARS-CoV-2 proteins are capable of modulating host innate immunity and type interferon responses, with this information serves to warrant further studies on SARS-CoV-2 pathogenesis.
- Xiaobo Lei
- , Xiaojing Dong
- & Jianwei Wang
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Article
| Open AccessDual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen
Studying emerging pathogens is often challenging due to the lack of information. Here the authors show that dual RNA-seq, profiling the host and pathogen transcriptome simultaneously, helps uncovering the biology of Orientia tsutsugamushi, a major cause of febrile illness in South-East Asia, and its interaction with the host.
- Bozena Mika-Gospodorz
- , Suparat Giengkam
- & Jeanne Salje
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Article
| Open AccessSingle cell transcriptomics reveals opioid usage evokes widespread suppression of antiviral gene program
Over 100 million of opioid prescriptions are issued yearly in the USA alone, but the impact of opioid use on the immune system is barely characterized. Here the authors report antiviral immune response is blunted in several types of blood cells from opioid-dependent individuals, and when healthy donor cells are exposed to morphine in a dish.
- Tanya T. Karagiannis
- , John P. Cleary Jr
- & Christine S. Cheng
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Article
| Open AccessLymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma
Nodular lymphocyte-predominant Hodgkin lymphoma with IgD+ lymphocyte-predominant (LP) cells is a rare clinical distinct lymphoma subset of B-cell origin. Here the authors show that antigens expressed by Moraxella catarrhalis are recognized by B cell receptors of IgD+ LP cells, suggesting the contribution of chronic antigen stimulation to lymphomagenesis.
- Lorenz Thurner
- , Sylvia Hartmann
- & Michael Pfreundschuh
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Article
| Open AccessFecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity
Sepsis due to multidrug resistant pathogens is the most common cause of death in intensive care units. Here, the authors report that fecal microbiota transplant (FMT) can rescue mice from lethal sepsis of pathogens isolated from stool of a critically ill patient and show that FMT reverses the immunosuppressive effect induced by the pathogen community.
- Sangman M. Kim
- , Jennifer R. DeFazio
- & John C. Alverdy
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Article
| Open AccessPhagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity
Macrophages undergo a Warburg-like switch from oxidative phosphorylation to glycolysis in response to inflammatory stimulus. Here the authors show that fungal melanin can trigger this switch in human macrophages by sequestering calcium in the phagosome and enabling protection against Aspergillus fumigatus infection.
- Samuel M. Gonçalves
- , Cláudio Duarte-Oliveira
- & Agostinho Carvalho
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Article
| Open AccessTAGAP instructs Th17 differentiation by bridging Dectin activation to EPHB2 signaling in innate antifungal response
TAGAP gene variants are linked to human autoimmunity. Here the authors identify TAGAP as a Dectin-1 and EphB2-binding protein mediating antifungal innate immune signaling and cytokine production, and demonstrate TAGAP in non-T cells promotes Th17 response in mouse models of infection and autoimmunity.
- Jianwen Chen
- , Ruirui He
- & Chenhui Wang
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Article
| Open AccessPerinatal inflammation influences but does not arrest rapid immune development in preterm babies
The infant immune system is continuously shaped by environmental factors. Here the authors demonstrate that rapid immune development in preterm babies is modulated by perinatal inflammation more than gut microbiota, and that lower CXCL8-producing T cells may identify infants susceptible to infection.
- S. Kamdar
- , R. Hutchinson
- & D. L. Gibbons
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Article
| Open AccessDynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection
Here, using longitudinal pre- and post-infection samples from the RV217 Early Capture HIV Cohort Study, the authors show that mucosa-associated invariant T (MAIT) cells become activated and expand during the early acute phase of HIV infection, with subsequent reprogramming towards innate-like functionality.
- Kerri G. Lal
- , Dohoon Kim
- & Johan K. Sandberg
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Article
| Open AccessOsteoprotegerin-dependent M cell self-regulation balances gut infection and immunity
Microfold cells (M cells) sit at the gut epithelial surface to sample antigens and maintain local immune homeostasis. Here the authors show that M cells are feedback-regulated by M cell-originated osteoprotegerin (OPG) to suppress RNAKL-induced M cell differentiation, and that OPG deficiency alters both gut colitis and infection phenotypes.
- Shunsuke Kimura
- , Yutaka Nakamura
- & Koji Hase
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Article
| Open AccessChallenging immunodominance of influenza-specific CD8+ T cell responses restricted by the risk-associated HLA-A*68:01 allomorph
The HLA-A*68:01 allele has been associated with severe influenza disease during the 2009 influenza pandemic. Here, the authors analyze influenza nucleoprotein specific HLA-A*68:01-restricted CD8+ T cells from human donors and show immunodominance of these cells in approximately 35% of HLA-A*68:01-expressing donors.
- C. E. van de Sandt
- , E. B. Clemens
- & K. Kedzierska
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Article
| Open AccessDistinct CD1d docking strategies exhibited by diverse Type II NKT cell receptors
Natural killer T (NKT) cells include type I that express semi-invariant T cell receptor (TCR), and type II that cover a broader repertoire. Here the authors describe the crystal structure of a type II NKT TCR complexed with CD1d/antigen to propose that type II NKT TCRs may adapt multiple CD1d docking modes to maximise antigen recognition efficacy.
- Catarina F. Almeida
- , Srinivasan Sundararaj
- & Jamie Rossjohn
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Article
| Open AccessPhagocytosis is mediated by two-dimensional assemblies of the F-BAR protein GAS7
The Bin/Amphiphysin/Rvs167 (BAR) domain superfamily, which includes FCH-BAR (F-BAR) domain proteins are membrane-sculpting proteins. Here the authors combine a range of techniques and show that the F-BAR domain of growth-arrest specific protein 7 (GAS7) forms two-dimensional sheets on flat membranes and that these oligomeric assemblies of GAS7 are required for the formation of phagocytic cups in macrophages.
- Kyoko Hanawa-Suetsugu
- , Yuzuru Itoh
- & Shiro Suetsugu
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Article
| Open AccessIFN-γ selectively suppresses a subset of TLR4-activated genes and enhancers to potentiate macrophage activation
Macrophage activation is synergistically controlled by lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Here the authors show that IFN-γ promotes macrophage activation not only by activating STAT1-dependent genes, but also by suppressing STAT3-dependent negative feedback regulation downstream of LPS signaling.
- Kyuho Kang
- , Mahesh Bachu
- & Lionel B. Ivashkiv
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Article
| Open AccessThe longevity-promoting factor, TCER-1, widely represses stress resistance and innate immunity
Resistance to stress is often associated with increased longevity. Using the model organism C. elegans the authors here show that TCER-1 enhances lifespan while at the same time increasing sensitivity to a number of biotic and abiotic stressors.
- Francis R. G. Amrit
- , Nikki Naim
- & Arjumand Ghazi
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Article
| Open AccessInduction of memory-like dendritic cell responses in vivo
Wormley and colleagues present data showing that vaccine strategies can be devised to prime dendritic cells to respond in a memory-like fashion upon subsequent exposure to a pathogen.
- Camaron R. Hole
- , Chrissy M. Leopold Wager
- & Floyd L. Wormley Jr.
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Article
| Open AccessA toll-like receptor agonist mimicking microbial signal to generate tumor-suppressive macrophages
Turning tumour promoting macrophages into an anti-tumour phenotype is an attractive therapeutic strategy. Here, the authors develop a polysaccharide-based structure that mimicks pathogen-associated molecular patterns and, by activating the toll-like receptors on macrophage surface, promotes a safe anti-tumour immune response in mouse models.
- Yanxian Feng
- , Ruoyu Mu
- & Chunming Wang
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Article
| Open AccessPhysical and functional interaction between A20 and ATG16L1-WD40 domain in the control of intestinal homeostasis
Maintaining the intestinal barrier function requires a balance of multiple signalling pathways. Here the authors show that A20, an anti-inflammatory and anti-apoptotic protein, and Atg1611, an autophagy regulator, cross-regulate their respective protein levels and function to serve compensatory and redundant roles in fine-tuning gut barrier homeostasis.
- Karolina Slowicka
- , Inmaculada Serramito-Gómez
- & Geert van Loo
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Article
| Open AccessMicrobial recognition by GEF-H1 controls IKKε mediated activation of IRF5
The transcription factor IRF5 is essential for immune defense against pathogens. Here, the authors show that the microtubule-associated factor GEF-H1 plays a critical role in host defense against Listeria monocytogenes in macrophages via activation of the IRF5 kinase IKKε.
- Yun Zhao
- , Rachid Zagani
- & Hans-Christian Reinecker
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Article
| Open AccessMacrophage achieves self-protection against oxidative stress-induced ageing through the Mst-Nrf2 axis
Immune cells produce reactive oxygen species (ROS) to eliminate pathogens, but cell-spontaneous death and ageing may also be induced. Here the authors show that, upon sensing ROS, Mst1/2 kinases modulate the activity of Nrf2 transcription factor and downstream genetic programs to protect mouse macrophages from death and ageing.
- Ping Wang
- , Jing Geng
- & Lanfen Chen
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Article
| Open AccessA child with perinatal HIV infection and long-term sustained virological control following antiretroviral treatment cessation
Some perinatally HIV infected children who have received early antiretroviral therapy (ART) show long-term sustained virological control after ART cessation. Here the authors describe a case who, at age 9.5 years, shows normal CD4:CD8 T cell ratios and has no detectable levels of replication-competent virus.
- Avy Violari
- , Mark F. Cotton
- & Caroline T. Tiemessen
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Article
| Open AccessRegulation of mycobacterial infection by macrophage Gch1 and tetrahydrobiopterin
Inducible nitric oxide (NO) synthase (iNOS) is essential in the response to mycobacterial infection, yet NOS signalling can occur through NO-dependent or NO-independent pathways. Here the authors show macrophage Gch1 and tetrahydrobiopterin mediate NO-independent control of Mycobacterial infection.
- Eileen McNeill
- , Elena Stylianou
- & Keith M. Channon
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Article
| Open AccessProteasomal degradation of NOD2 by NLRP12 in monocytes promotes bacterial tolerance and colonization by enteropathogens
Mutations in nucleotide-binding oligomerization domain protein 12 (NLRP12) are known to effect inflammatory processes. Here the authors show that NLRP12-mediated proteasomal degradation of NOD2 in monocytes promotes bacterial tolerance and colonisation in a model of enteric infection.
- Sylvain Normand
- , Nadine Waldschmitt
- & Mathias Chamaillard
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Article
| Open AccessControl of Treg cell homeostasis and immune equilibrium by Lkb1 in dendritic cells
Regulatory T (Treg) cells are important for maintaining immune homeostasis by suppressing immune cell activation, but how the Treg cell pool is maintained is still unclear. Here the authors show that a kinase, Lkb1, operates in dendritic cells (DC) to inhibit Treg cell expansion and immunosuppression via mechanisms involving NF-kB/OX40L signalling.
- Song Chen
- , Lijun Fang
- & Xiaoming Feng
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Article
| Open AccessBirth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential
The effects of caesarean section delivery on mother-to-neonate transmission of microbiota are unclear. Here the authors show that caesarean section delivery can affect the transmission of specific microbial strains and the immunomodulatory potential of the microbiota.
- Linda Wampach
- , Anna Heintz-Buschart
- & Paul Wilmes
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Article
| Open AccessThe deubiquitinase MYSM1 dampens NOD2-mediated inflammation and tissue damage by inactivating the RIP2 complex
The innate immune receptor NOD2 is tightly regulated to ensure beneficial antimicrobial immunity. Here the authors show that the H2A deubiquitinase MYSM1 restrains NOD2 signaling by removing lysine 63 (K63), K27, M1 but not K48 polyubiquitin chains from its downstream adaptor protein RIP2.
- Swarupa Panda
- & Nelson O. Gekara
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Article
| Open AccessA homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease
Mutations in genes encoding NAPDH oxidase subunits are known to be causative for the primary immunodeficiency chronic granulomatous disease (CGD). Here, the authors identify CYBC1 mutations in patients with CGD and show that CYBC1 is important for formation of the NADPH complex and respiratory burst.
- Gudny A. Arnadottir
- , Gudmundur L. Norddahl
- & Kari Stefansson