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| Open AccessNFκB and NLRP3/NLRC4 inflammasomes regulate differentiation, activation and functional properties of monocytes in response to distinct SARS-CoV-2 proteins
The immunobiology regulating the contribution of monocytes to severe COVID-19 immunopathology are not fully understood. Here the authors show that SARS-CoV-2 S1 and NP proteins differentially promote NLRP3/NLRC4 inflammasome activity, differentiation, and T cell-priming function of monocytes.
- Ilya Tsukalov
- , Ildefonso Sánchez-Cerrillo
- & Enrique Martin-Gayo
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| Open AccessGene expression analyses reveal differences in children’s response to malaria according to their age
Here the authors use dual RNA sequencing to characterize host and parasite gene expression from 136 Malian children with symptomatic Plasmodium falciparum infection. They find that parasitemia levels correlate with neutrophil and T cell levels and that the child’s age correlates with innate immune gene expression as well as gametocyte levels.
- Kieran Tebben
- , Salif Yirampo
- & David Serre
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| Open AccessNeuronal miR-9 promotes HSV-1 epigenetic silencing and latency by repressing Oct-1 and Onecut family genes
Here, the authors identify neuron-specific miR-9 that potentially blocks HSV-1 neuronal replication by targeting host OCT-1 and ONECUT transcription factors involved in epigenetic activation of HSV-1 productive-cycle genes. Thus miR-9 promotes viral epigenetic silencing and latent infection in neurons.
- Yue Deng
- , Yuqi Lin
- & Dongli Pan
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| Open AccessCoordinated inflammatory responses dictate Marburg virus control by reservoir bats
The authors show pro-inflammatory responses are needed for Marburg virus control in its natural bat reservoir, and that if reduced, humanlike disease and shedding results, suggesting that natural immunomodulatory stressors may increase spillover risk.
- Jonathan C. Guito
- , Shannon G. M. Kirejczyk
- & Jonathan S. Towner
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Article
| Open AccessBTLA contributes to acute-on-chronic liver failure infection and mortality through CD4+ T-cell exhaustion
Acute-on-chronic liver failure (ACLF) is characterized by rapid deterioration of liver function in patients with chronic liver disease. Here, the authors show that BTLA expression in CD4+ T cells is associated with disease severity and inflammation in hepatitis B virus-related ACLF.
- Xueping Yu
- , Feifei Yang
- & Jiming Zhang
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Article
| Open AccessQ586B2 is a crucial virulence factor during the early stages of Trypanosoma brucei infection that is conserved amongst trypanosomatids
Sleeping sickness caused by African trypanosome parasites induces a chronic, and potentially lethal, infection in humans. Here, the authors uncover a conserved protein, Q586B2, playing an important regulatory role in Trypanosomatid infection establishment.
- Benoit Stijlemans
- , Patrick De Baetselier
- & Carl De Trez
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Article
| Open AccessGlobal fungal-host interactome mapping identifies host targets of candidalysin
Candidalysin is a toxin secreted by Candida albicans. Although critical for pathogenesis, its intracellular targets are not well mapped. Here, Zhang et al screen for interacting proteins and identify that candidalysin can modulate the DNA damage repair pathway to promote fungal infection.
- Tian-Yi Zhang
- , Yao-Qi Chen
- & Ning-Ning Liu
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| Open AccessPersistence in risk and effect of COVID-19 vaccination on long-term health consequences after SARS-CoV-2 infection
The long-term health consequences of COVID-19 infection are not fully understood. In this retrospective cohort study from Hong Kong, the authors describe changes in the risk of various clinical outcomes including all-cause mortality for one year following COVID-19 infection and how they vary by vaccination status.
- Ivan Chun Hang Lam
- , Ran Zhang
- & Eric Yuk Fai Wan
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Article
| Open AccessNucleocapsid protein-specific monoclonal antibodies protect mice against Crimean-Congo hemorrhagic fever virus
There are limited treatment options for infection with Crimean-Congo hemorrhagic fever virus in humans. Here, the authors show that a monoclonal antibody targeting the highly conserved viral nucleocapsid protein provides protective effects in a mouse model of infection.
- Aura R. Garrison
- , Vanessa Moresco
- & Joseph W. Golden
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Article
| Open AccessPrior flavivirus immunity skews the yellow fever vaccine response to cross-reactive antibodies with potential to enhance dengue virus infection
Flavivirus infection or vaccination can induce cross-reactive immune responses. Here, the authors show how previous immunization with the tick-borne encephalitis virus vaccine affects the immune response to the yellow fever vaccine, suggesting that the yellow fever vaccine virus conceals epitopes shared with other flaviviruses in flavivirus-naive but not flavivirus-pre-exposed individuals.
- Antonio Santos-Peral
- , Fabian Luppa
- & Simon Rothenfusser
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| Open AccessImmune signature of Chlamydia vaccine CTH522/CAF®01 translates from mouse-to-human and induces durable protection in mice
Authors present a comparative immunological characterisation of Chlamydia vaccine, CTH522/CAF®01, in mice and humans. Findings suggest the mouse to be a good predictor of human immunity to the Chlamydia vaccine CTH522/CAF®01, and long-lasting protection in the mouse further supports the development of this promising vaccine candidate.
- Anja W. Olsen
- , Ida Rosenkrands
- & Frank Follmann
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Article
| Open AccessTcrXY is an acid-sensing two-component transcriptional regulator of Mycobacterium tuberculosis required for persistent infection
Stupar et al. describe a new role for the Mycobacterium tuberculosis two-component system, TcrXY, in the modulation of up to 70 genes, including two effectors, TarA and TarB which mitigate intracellular redox stress.
- Miljan Stupar
- , Lendl Tan
- & Nicholas P. West
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Article
| Open AccessThe plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete plasmid assemblies
Plasmids carry antimicrobial resistance genes and contribute to the rapid dissemination of resistance. Here, the authors sequence 1,880 complete plasmids from 738 isolates from bloodstream infections, shedding light on the links between plasmid types, bacterial hosts and antimicrobial resistance.
- Samuel Lipworth
- , William Matlock
- & Nicole Stoesser
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| Open AccessDeep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome
Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined and the pathophysiology unknown. Here, the authors conduct deep phenotyping of a cohort of PI-ME/CFS patients.
- Brian Walitt
- , Komudi Singh
- & Avindra Nath
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| Open AccessGlobal evaluation of lineage-specific human papillomavirus capsid antigenicity using antibodies elicited by natural infection
Human Papillomaviruses (HPV) are classified in lineages based on their sequence. Here, the authors test neutralizing activity of sera from naturally infected women against vaccine-preventable HPV variants, delineating lineage-specific antibody responses.
- Gathoni Kamuyu
- , Filomeno Coelho da Silva
- & Simon Beddows
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| Open AccessA convergent evolutionary pathway attenuating cellulose production drives enhanced virulence of some bacteria
Extra-intestinal pathogenic Escherichia coli cause urinary tract and bloodstream infections. Here, the authors show how mutations that disrupt the production of cellulose, a polysaccharide produced by many bacteria, drive enhanced virulence.
- Nguyen Thi Khanh Nhu
- , M. Arifur Rahman
- & Mark A. Schembri
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| Open AccessCOVID-19 immune signatures in Uganda persist in HIV co-infection and diverge by pandemic phase
Less is known about SARS-CoV-2 infection in unstudied geographical areas such as sub-Saharan Africa. Here the authors use multi-omics to characterize the immune response to SARS-CoV-2 in Uganda and consider how people living with HIV immunologically differentially respond to the virus.
- Matthew J. Cummings
- , Barnabas Bakamutumaho
- & Max R. O’Donnell
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| Open AccessFlexible and cost-effective genomic surveillance of P. falciparum malaria with targeted nanopore sequencing
Genomic surveillance of Plasmodium falciparum could improve monitoring of drug resistance, but implementation has been hampered due to the large and complex genome. Here, de Cesare et al. develop a flexible and cost-effective nanopore sequencing approach to detect drug resistance and diagnostic escape for P. falciparum malaria.
- Mariateresa de Cesare
- , Mulenga Mwenda
- & Jason A. Hendry
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| Open AccessAssessing emergence risk of double-resistant and triple-resistant genotypes of Plasmodium falciparum
Emergence of malaria parasites resistant to artemisinin has prompted the need for new drug regimens to ensure effective treatment. In this simulation study, the authors evaluate the risk of multidrug resistance under regimens with either concurrent or cyclic use of different first-line therapies.
- Eric Zhewen Li
- , Tran Dang Nguyen
- & Maciej F. Boni
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| Open AccessTGF-β blockade drives a transitional effector phenotype in T cells reversing SIV latency and decreasing SIV reservoirs in vivo
Treatment with the clinical stage TGF-β inhibitor galunisertib promotes latency reversal of HIV/SIV. Here, using a treatment regimen similar to the one tested in clinical trials, the authors show how galunisertib affects immune cell function, increases SIV reactivation, and reduces the viral reservoir in macaques.
- Jinhee Kim
- , Deepanwita Bose
- & Elena Martinelli
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Article
| Open AccessNatural selection and genetic diversity maintenance in a parasitic wasp during continuous biological control application
Parasitoid wasps are reared and released as biocontrol agents to manage aphids and protect crops. Here, the authors use genomes from 542 wasps to show that, in spite of wide scale release of low-diversity captive individuals, diversity in wild populations is maintained.
- Bingyan Li
- , Yuange Duan
- & Hu Li
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Q&A
| Open AccessA spotlight on the tuberculosis epidemic in South Africa
Tuberculosis is the leading cause of death from a single infectious agent, with over 25% of these occurring in the African region. Multi-drug resistant strains which do not respond to first-line antibiotics continue to emerge, putting at risk numerous public health strategies which aim to reduce incidence and mortality. Here, we speak with Professor Valerie Mizrahi, world-leading researcher and former director of the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town, regarding the tuberculosis burden in South Africa. We discuss the challenges faced by researchers, the lessons that need to be learnt and current innovations to better understand the overall response required to accelerate progress.
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| Open AccessIncome determines the impact of cash transfers on HIV/AIDS: cohort study of 22.7 million Brazilians
Brazil has operated a conditional cash transfer program to support families living in precarious conditions since 2004. Here, the authors use linked administrative and health data to investigate the impacts of the program on HIV/AIDS-related outcomes, demonstrating strong positive associations.
- Andréa F. Silva
- , Inês Dourado
- & Davide Rasella
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| Open AccessApplying valency-based immuno-selection to generate broadly cross-reactive antibodies against influenza hemagglutinins
Here the authors develop a DNA vaccine, mixing 18 hemagglutinin (HA) subtypes monovalently into heterodimeric molecules, and show that it induces broadly reactive antibodies against subdominant HA epitopes and heterologous protection against influenza A viruses in mice.
- Daniëla Maria Hinke
- , Ane Marie Anderson
- & Ranveig Braathen
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| Open AccessA hepatic network of dendritic cells mediates CD4 T cell help outside lymphoid organs
Here, English et al. show that after expanding in lymphoid tissues, CD4+ and CD8+ T cells recognising hepatic antigens migrate into specialised vascular liver areas where CD4+ T cells locally license hepatic dendritic cells and further expand CD8+ T cell numbers.
- Kieran English
- , Rain Kwan
- & Patrick Bertolino
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| Open AccessComparative effectiveness of alternative intervals between first and second doses of the mRNA COVID-19 vaccines
The optimal timing between first and second mRNA COVID-19 vaccine doses has not been established. Here, the authors use electronic health record data from Georgia, USA in a target trial emulation study to estimate vaccine effectiveness against infection for different dose intervals.
- Kayoko Shioda
- , Alexander Breskin
- & Elizabeth T. Rogawski McQuade
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| Open AccessThe role of extracellular vesicle fusion with target cells in triggering systemic inflammation
Extracellular vesicles (EVs) play a crucial role in intercellular communication by transferring bioactive molecules from donor to recipient cells. Here, the authors show that EVs play a crucial role in activating immune responses through cell fusion, shedding light on their impact on inflammation.
- Praveen Papareddy
- , Ines Tapken
- & Heiko Herwald
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| Open AccessPredicting the risk and speed of drug resistance emerging in soil-transmitted helminths during preventive chemotherapy
Resistance to chemotherapy for soil-transmitted helminth infection has been detected in veterinary settings but not yet in human infections. Here, the authors investigate the risk of resistance in humans and how it may change as a result of scaling-up preventative deworming programs.
- Luc E. Coffeng
- , Wilma A. Stolk
- & Sake J. de Vlas
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| Open AccessMAIVeSS: streamlined selection of antigenically matched, high-yield viruses for seasonal influenza vaccine production
Vaccines combat global influenza threats, relying on timely selection of optimal seed viruses. Here, authors introduce MAIVeSS, a machine learning assisted framework to streamline vaccine seed virus selection using genomic sequence, expediting seasonal flu vaccine production and supply.
- Cheng Gao
- , Feng Wen
- & Xiu-Feng Wan
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Article
| Open AccessSynchrony of Bird Migration with Global Dispersal of Avian Influenza Reveals Exposed Bird Orders
Highly pathogenic avian influenza virus subtype H5 is an important pathogen of wild birds and poultry that has also caused infection in humans and other mammals. Here the authors use wild bird movement tracking data and virus genome sequences to quantify how seasonal bird migration facilitates global dispersal of the virus.
- Qiqi Yang
- , Ben Wang
- & Bryan Grenfell
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Article
| Open AccessA monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity
Characterisation of monoclonal antibodies against SARS-CoV-2 are useful for potential therapeutics or to understand more about the immune response to this virus. Here the authors characterise a monoclonal antibody that has a broad range of reactivity against SARS-CoV-2 variants and measure how it binds to its specific target region of the receptor binding domain.
- Leire de Campos-Mata
- , Benjamin Trinité
- & Giuliana Magri
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Article
| Open AccessBystander activated CD8+ T cells mediate neuropathology during viral infection via antigen-independent cytotoxicity
Many viral infections are linked to the development of neurological disorders. Here, Balint et al use a mouse model of Zika virus infection to show that it is immune cells (NKG2D+CD8+ T cells) that cause infection-associated paralysis, rather than the virus itself.
- Elizabeth Balint
- , Emily Feng
- & Ali A. Ashkar
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Article
| Open AccessHIV-associated gut microbial alterations are dependent on host and geographic context
Here, the authors compare the fecal microbial community of individuals in the U.S., Uganda, and Botswana, and identify significant bacterial taxa alterations with both treated and untreated HIV infection although with a high degree of uniqueness in each cohort, and also significant differences between populations that report men who have sex with men (MSM) behavior and non-MSM populations.
- Muntsa Rocafort
- , David B. Gootenberg
- & Douglas S. Kwon
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Article
| Open AccessGestational diabetes augments group B Streptococcus infection by disrupting maternal immunity and the vaginal microbiota
Here, Marcado-Evans et al show that gestational diabetes enhances group B Streptococcus infection through altering host-microbe dynamics, disrupting maternal immunity, and perturbing the vaginal microbiota in a murine pregnancy model.
- Vicki Mercado-Evans
- , Marlyd E. Mejia
- & Kathryn A. Patras
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| Open AccessRisk of SARS-CoV-2 reinfection during multiple Omicron variant waves in the UK general population
The factors influencing risk of reinfection with SARS-CoV-2 are poorly understood. Here, the authors use data from the UK COVID-19 Infection Survey, a community based longitudinal study, to assess characteristics of ~45,000 reinfections compared to initial infections.
- Jia Wei
- , Nicole Stoesser
- & Chris Cunningham
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| Open AccessMaternal pertussis immunization and the blunting of routine vaccine effectiveness: a meta-analysis and modeling study
Pertussis immunisation for pregnant women has been introduced to protect newborns, but immunological evidence suggests that this lessens subsequent infant immune response to vaccination. Here, the authors assess the epidemiological impacts of both consequences of maternal immunisation on infant infection.
- Michael Briga
- , Elizabeth Goult
- & Matthieu Domenech de Cellès
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Article
| Open AccessDimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.
- Peter Sandercock
- , Janet Darbyshire
- & Martin J. Landray
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| Open AccessHumoral profiles of toddlers and young children following SARS-CoV-2 mRNA vaccination
Nziza et al. profile anti-SARS-CoV-2 antibody responses in infants and toddlers after mRNA vaccination and demonstrate a strong functional activation of humoral immunity in this age group when compared with adults and naturally infected children.
- Nadège Nziza
- , Yixiang Deng
- & Lael M. Yonker
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| Open AccessA nanoparticle-based sonodynamic therapy reduces Helicobacter pylori infection in mouse without disrupting gut microbiota
Here, the authors develop a non-antibiotic approach using sonodynamic therapy mediated by a lecithin bilayer-coated poly(lactic-co-glycolic) nanoparticle preloaded with verteporfin, Ver-PLGA@Lecithin, to treat Helicobacter pylori.
- Tao Liu
- , Shuang Chai
- & Lihua Yang
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Article
| Open AccessPRL2 regulates neutrophil extracellular trap formation which contributes to severe malaria and acute lung injury
Excessive inflammatory responses contribute to severe malaria. Here, Du et al, show that the protein tyrosine phosphatase PRL2 contributes to neutrophil activation and extracellular trap release in an experimental model of severe malaria.
- Xinyue Du
- , Baiyang Ren
- & Zhaojun Wang
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Article
| Open AccessIdentification of differentially recognized T cell epitopes in the spectrum of tuberculosis infection
T cells play critical roles in the immune pathology of tuberculosis. Here the authors perform a proteome-wide screen of T cell antigens and reactivity to mycobacterium tuberculosis at different stages of infection.
- Sudhasini Panda
- , Jeffrey Morgan
- & Cecilia S. Lindestam Arlehamn
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Article
| Open AccessUBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors
The RIG-I like receptors sense RNA viruses and initiate antiviral immunity. Here the authors screen 375 definite ubiquitin ligases and propose UBR5 promotes RLR transcription by disengaging the TRIM28-imposed brake on the RLR promoters.
- Duomeng Yang
- , Tingting Geng
- & Penghua Wang
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| Open AccessInvestigating the etiologies of non-malarial febrile illness in Senegal using metagenomic sequencing
Non-malarial febrile illnesses have a range of potential aetiologies which are difficult to diagnose and therefore treat. Here, the authors investigate the causes of acute febrile illness in a peri-urban area of Senegal with low malaria incidence using untargeted and targeted sequencing methods.
- Zoë C. Levine
- , Aita Sene
- & Katherine J. Siddle
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| Open AccessRespiratory distress in SARS-CoV-2 exposed uninfected neonates followed in the COVID Outcomes in Mother-Infant Pairs (COMP) Study
Unusually high rates of respiratory distress were observed in infants following in utero exposure to SARS-CoV-2. Here the authors find, in a longitudinal cohort of infants born to persons infected with SARS-CoV-2 during pregnancy, that maternal vaccination is associated with a lower odds of infant respiratory distress.
- Olivia M. Man
- , Tamiris Azamor
- & Karin Nielsen-Saines
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| Open AccessAn IL-10/DEL-1 axis supports granulopoiesis and survival from sepsis in early life
Neutrophils play critical roles in response to infection, and the limit of available neutrophils in neonates and young infants can impact responses to infections, including sepsis. Here the authors identify that the IL-10/DEL-1 axis is involved in emergency granulopoiesis in neonates and suggest a link to sepsis survival in early life.
- Eleni Vergadi
- , Ourania Kolliniati
- & Christos Tsatsanis
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| Open AccessShifting patterns of dengue three years after Zika virus emergence in Brazil
Dengue virus circulation was unusually low in Brazil in 2015-2018 following the emergence of Zika virus, but subsequently resurged causing large outbreaks with a lower mean age of infection. Here, the authors use mathematical modelling to investigate the links between dengue dynamics and prior Zika infection.
- Francesco Pinotti
- , Marta Giovanetti
- & José Lourenço
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| Open AccessLongitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity
Single cell transcriptomics can reveal at high resolution the body’s response to infection. Here the authors have applied this technology to a longitudinal SARS-CoV-2 infected cohort and identified gene expression changes that may predict disease severity and reveal the underlying molecular mechanisms.
- Quy Xiao Xuan Lin
- , Deepa Rajagopalan
- & Shyam Prabhakar
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| Open AccessDeterminants of epidemic size and the impacts of lulls in seasonal influenza virus circulation
Seasonal influenza levels were unusually low when non-pharmaceutical interventions for COVID-19 were in place. Here, the authors analyse serological and epidemiological evidence for the hypothesis that such lulls in influenza transmission lead to reduced immunity and therefore larger epidemics in subsequent seasons.
- Simon P. J. de Jong
- , Zandra C. Felix Garza
- & Colin A. Russell
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| Open AccessRisk of COVID-19 death in adults who received booster COVID-19 vaccinations in England
Ward et al. utilise electronic health records to identify groups of adults (who had received a second booster dose of a COVID-19 vaccine) at elevated risk of COVID-19 death.
- Isobel L. Ward
- , Chris Robertson
- & Vahé Nafilyan