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Improvement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection
Post-acute sequelae of COVID (PASC) or long-COVID can affect a proportion of those infected but this is not well understood. Here the authors perform a single cell transcriptomics analysis of immune cells from long-COVID patients at 24 months and find that cell changes observed at 3 and 8 months do not persist to 24 months.
- Chansavath Phetsouphanh
- , Brendan Jacka
- & Gail V. Matthews
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Early-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice
Exercise could affect the immune system, but whether early-life exercise could benefit immune health in adulthood is not fully understood. Here the authors show that early-life exercise promotes epi-metabolic changes in the liver to potentially benefit immunity in older age and characterise the involvement of pipecolic acid in this process.
- Nini Zhang
- , Xinpei Wang
- & Feng Gao
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Potent human neutralizing antibodies against Nipah virus derived from two ancestral antibody heavy chains
Nipah virus is a WHO priority pathogen, and there is currently no approved drug for clinical therapy. Here, the authors identified potent human neutralizing antibodies that block receptor binding and provide protection against NiV infection in vivo.
- Li Chen
- , Mengmeng Sun
- & Sandra Chiu
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Autophagy-enhancing ATG16L1 polymorphism is associated with improved clinical outcome and T-cell immunity in chronic HIV-1 infection
T cell dysregulation is a hallmark of chronic HIV-1 infection that is partially restored by antiretroviral therapy. Here the authors show that ATG16L1 rs6861 polymorphism is associated clinically with prolonged control of disease pathogenesis, and functionally with enhanced autophagy and T-cell immunity in chronically HIV-1 infected individuals.
- Renée R. C. E. Schreurs
- , Athanasios Koulis
- & Carla M. S. Ribeiro
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Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI
Catheter-associated urinary tract infections can often lead to secondary bloodstream infections, and catheter-induced bladder inflammation. In this work, authors utilise murine models to probe defective fibrinolysis drives extravascular fibrin formation, potentially predisposing hosts to severe CAUTI.
- Jonathan J. Molina
- , Kurt N. Kohler
- & Ana L. Flores-Mireles
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Prior infection with unrelated neurotropic virus exacerbates influenza disease and impairs lung T cell responses
Co-infections are much less studied than single pathogen infections. Here, the authors show that co-infection with two unrelated viruses, neurotropic Semliki Forest virus and influenza A virus, exacerbates influenza-related lung pathology and prolongs lung virus replication in a mouse model.
- Isabelle Jia-Hui Foo
- , Brendon Y. Chua
- & Lukasz Kedzierski
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Mutations in the efflux pump regulator MexZ shift tissue colonization by Pseudomonas aeruginosa to a state of antibiotic tolerance
Mutations in mexZ, encoding a negative regulator of efflux pump genes, are frequently acquired by Pseudomonas aeruginosa during early lung infection, but do not confer high antibiotic resistance as measured in lab tests. Here, Laborda et al. show that mexZ mutations affect quorum sensing pathways, thus promoting tissue invasiveness and protecting bacteria from the action of antibiotics within tissues.
- Pablo Laborda
- , Signe Lolle
- & Helle Krogh Johansen
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Parechovirus infection in human brain organoids: host innate inflammatory response and not neuro-infectivity correlates to neurologic disease
In comparison to PeV-A1, infection with PeV-A3 is associated with neurological illness in infants. Here, using brain organoids, the authors suggest that the innate inflammatory response as the underlying reason, and not replication kinetics.
- Pamela E. Capendale
- , Inés García-Rodríguez
- & Katja C. Wolthers
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Rapid evolution of an adaptive multicellular morphology of Candida auris during systemic infection
Bing et al. report that Candida auris undergoes rapid evolution via de novo genetic mutations and forms multicellular aggregates that exhibit a survival advantage over the single-celled yeast-form phenotype during host infection.
- Jian Bing
- , Zhangyue Guan
- & Guanghua Huang
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Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation
There is limited data on immune factors contributing to SARS-CoV-2 viral clearance in people living with HIV. Here, the authors show that re-emergence of the neutralizing antibody response may be key to clearing persistent SARS-CoV-2 infection in ART-mediated recovery from immunosuppression in advanced HIV disease.
- Farina Karim
- , Catherine Riou
- & Alex Sigal
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Bacteriophage DNA induces an interrupted immune response during phage therapy in a chicken model
Bacteriophage are potential therapeutics to target bacterial infections, but recent studies suggest that bacteriophage may induce immune responses in eukaryotic cells. Here the authors show that bacteriophage DNA induces interrupted host immunity in a chicken infection model.
- Magdalena Podlacha
- , Lidia Gaffke
- & Alicja Węgrzyn
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Antiviral responses induced by Tdap-IPV vaccination are associated with persistent humoral immunity to Bordetella pertussis
Epidemics of whooping cough caused by Bordetella pertussis have been seen and are linked to waning immunity globally. Here the authors explore responses to inactivated poliovirus (IPV) in the Tdap-IPV vaccine and show it stimulates early antiviral responses in monocytes and dendritic cells that are associated with long-lived pertussis antibody responses.
- Joshua Gillard
- , Madeleine Suffiotti
- & Dimitri A. Diavatopoulos
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Global 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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S-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogens
The generation of reactive oxygen and nitrogen species is an critical part of host defense against microbial infection. Here, Jia et al, characterize the mechanisms by which reactive nitrogen species can modulate innate immunity.
- Mutian Jia
- , Li Chai
- & Wei Zhao
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COVID-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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Mosquito midgut stem cell cellular defense response limits Plasmodium parasite infection
Here, the authors study the cellular response of midgut progenitors in Anopheles stephensi to Plasmodium berghei infection. They show that midgut stem cells are able to detect Plasmodium oocysts and eliminate them in a Jak/STAT pathway dependent manner.
- Ana-Beatriz F. Barletta
- , Jamie C. Smith
- & Carolina Barillas-Mury
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T-bet+ B cells are activated by and control endogenous retroviruses through TLR-dependent mechanisms
Endogenous retroviruses (ERV) can induce immune responses and the control of these viruses uses immune mechanisms also involved in autoimmunity. Here, the authors characterize the control of ERVs in mice and show age-associated B cell control and nucleic acid sensing TLR pathway involvement.
- Eileen Rauch
- , Timm Amendt
- & Philipp Yu
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The 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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Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds
Three-dimensional DNA origami constructs can be used to deliver vaccine antigens in a multi-valent form. Here the authors design a DNA origami system for SARS-CoV-2 proteins and characterize in mice the immune response and protective capacity of generated antibodies, finding that the construct itself is not immunogenic.
- Eike-Christian Wamhoff
- , Larance Ronsard
- & Mark Bathe
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A two-step activation mechanism enables mast cells to differentiate their response between extracellular and invasive enterobacterial infection
Mast cells serve as sentinels for mucosal infection. This study shows how mast cells can differentially detect extracellular and invasive gut bacteria, and in response tune their cytokine production to signal different levels of danger.
- Christopher von Beek
- , Anna Fahlgren
- & Mikael E. Sellin
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PRL2 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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Identification 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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EGFR core fucosylation, induced by hepatitis C virus, promotes TRIM40-mediated-RIG-I ubiquitination and suppresses interferon-I antiviral defenses
Alpha-(1,6)-fucosyltransferase (FUT8) is the sole enzyme responsible for core fucosylation of N-glycans during glycoprotein biosynthesis. Here the authors show that HCV envelope protein E2 enhances FUT8 expression through the EGFR-AKT-SNAIL axis, which subsequently promotes RIG-I K48-ubiquitination and dampens the antiviral IFN-I response through core fucosylated-EGFR-JAK1-STAT3-RIG-I pathway.
- Qiu Pan
- , Yan Xie
- & Xiao-Lian Zhang
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LOX-1 acts as an N6-methyladenosine-regulated receptor for Helicobacter pylori by binding to the bacterial catalase
N6-methyladenosine (m6A) modification of mRNA regulates gene expression in eukaryotes. Here, Zeng et al. show that m6A modification of mRNAs contributes to protection against the pathogen Helicobacter pylori by downregulating a host protein that acts as receptor for the pathogen.
- Judeng Zeng
- , Chuan Xie
- & William K. K. Wu
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Identifying immune signatures of sepsis to increase diagnostic accuracy in very preterm babies
Bacterial infections and sepsis are a major cause of mortality in preterm babies. Here Das and colleagues assess the paediatric immune response to bacterial infection in very preterm babies and identify blood immune markers that could improve accuracy of diagnostics to rule-out sepsis and guide antibiotic treatment.
- A. Das
- , G. Ariyakumar
- & D. L. Gibbons
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Direct translation of incoming retroviral genomes
A defining feature of retroviruses compared to other +ssRNA viruses is reverse transcription. Here, Köppke et al. show that retroviruses (e.g. HIV-1) can produce viral proteins even in the absence of reverse transcription.
- Julia Köppke
- , Luise-Elektra Keller
- & Oya Cingöz
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Alveolar macrophage-expressed Plet1 is a driver of lung epithelial repair after viral pneumonia
Influenza virus infection causes injury to the lung. Here, Pervizaj-Oruqaj et al. show that Plet1 expressed by lung macrophages promotes epithelial repair by boosting epithelial cell proliferation and barrier function.
- Learta Pervizaj-Oruqaj
- , Balachandar Selvakumar
- & Susanne Herold
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The Mycobacterium tuberculosis methyltransferase Rv2067c manipulates host epigenetic programming to promote its own survival
Singh et al. show how the M. tuberculosis methyltransferase Rv2067c outsmarts host epigenetic machinery by methylating histone H3 prior to its assembly into nucleosomes, thereby ensuring the pathogen’s intracellular survival/success.
- Prakruti R. Singh
- , Venkatareddy Dadireddy
- & Valakunja Nagaraja
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Intranasal mask for protecting the respiratory tract against viral aerosols
The spread of many infectious diseases substantially relies on aerosol transmission to the respiratory tract. Here, the authors design an intranasal mask with the ability to intercept viral aerosols, entrap and inactivate virus, thus preventing respiratory tract infection.
- Xiaoming Hu
- , Shuang Wang
- & Wei Wei
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Geometric constraint-triggered collagen expression mediates bacterial-host adhesion
Cells in the body live in geometrically constrained microenvironments. Here, Feng at al report that these constraints induce collagen IV expression which is responsible for location dependent bacterial adhesion.
- Yuting Feng
- , Shuyi Wang
- & Jianyong Huang
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| Open Access
RNA is a key component of extracellular DNA networks in Pseudomonas aeruginosa biofilms
The roles of extracellular RNAs present in bacterial biofilms are poorly understood. Here, Mugunthan et al. show that specific mRNAs associate with extracellular DNA in the matrix of bacterial biofilms, facilitating the formation of viscoelastic networks.
- Sudarsan Mugunthan
- , Lan Li Wong
- & Thomas Seviour
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Synthetic genetic oscillators demonstrate the functional importance of phenotypic variation in pneumococcal-host interactions
Here, Rueff et al engineered a CRISPRi-based oscillator to rewire capsule production in Streptococcus pneumoniae from its native control. They show that heterogeneity in capsule production is beneficial for fitness in several virulence associated traits.
- Anne-Stéphanie Rueff
- , Renske van Raaphorst
- & Jan-Willem Veening
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Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins
Here, Ning et al report the cellular interactomes of Crimean-Congo haemorrhagic fever virus glycoproteins and uncover a host restriction factor HAX1 that hijacks the viral glycoproteins to mitochondria, disabling progeny virion packaging.
- Shiyu Dai
- , Yuan-Qin Min
- & Yun-Jia Ning
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| Open Access
Microglia are not protective against cryptococcal meningitis
Cryptococcal meningitis is a life-threatening fungal infection. Here, Mohamed et al find that brain resident microglia do not provide protection against this infection and instead are a site where the fungus may access the micronutrient copper.
- Sally H. Mohamed
- , Man Shun Fu
- & Rebecca A. Drummond
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Tissue-resident B cells orchestrate macrophage polarisation and function
The function of B cells in peripheral blood and secondary lymphoid organs has long been appreciated but whether and how they contribute to tissue immune homeostasis is lesser known. Non-lymphoid organs harbour tissue-resident B cells that include a substantial population of B-1 cells and promote homeostatic anti-inflammatory macrophage polarization via IL-10, with profound effects on bacterial clearance during local infection.
- Ondrej Suchanek
- , John R. Ferdinand
- & Menna R. Clatworthy
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IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection
Trypanosome brucei is known to colonise the subcutaneous white adipose tissue and the interaction with the cellular locale could play key roles in pathogenesis and host response. Here the author’s use single cell approaches and in vivo animal models, and show a role for IL-17 in the adipose tissue response and parasite burden in a chronic murine model of infection.
- Matthew C. Sinton
- , Praveena R. G. Chandrasegaran
- & Juan F. Quintana
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| Open Access
HIV-1 diverts cortical actin for particle assembly and release
HIV-1 assembles and buds from the host cell membrane of infected T lymphocytes. Here, Dibsy et al. characterise the role of cortical actin, viral Gag and host factor Arpin in virion assembly and release.
- Rayane Dibsy
- , Erwan Bremaud
- & Delphine Muriaux
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| Open Access
Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming
Exhaustion is the functional deterioration of T cells following chronic stimulation. Here, Wu et al. show that mitochondrial dysfunction drives T cell exhaustion by inhibiting HIF-1α degradation and transcriptional metabolic reprogramming.
- Hao Wu
- , Xiufeng Zhao
- & Martin Vaeth
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Article
| Open Access
A single amino acid substitution in the capsid protein of Zika virus contributes to a neurovirulent phenotype
The neurovirulence determinants of Zika virus remain not fully established. Song et al identified a single K101R substitution in the capsid protein that contributes to the lineage-specific virulence phenotypes.
- Guang-Yuan Song
- , Xing-Yao Huang
- & Cheng-Feng Qin
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| Open Access
Localized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease
The impact of antiparasitic treatment on local tissue responses in the case of chronic Chagas disease (caused by Trypanosoma cruzi infection) is not well understood. Authors provide insight into clinical treatment failure and drivers of post-infectious conditions.
- Zongyuan Liu
- , Rebecca Ulrich vonBargen
- & Laura-Isobel McCall
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Article
| Open Access
Gut Bacteroides act in a microbial consortium to cause susceptibility to severe malaria
Specific gut microbiota constituents that affect the severity of malaria are unknown. Here, Mandal et al. identify specific Bacteroides species causing susceptibility to severe malaria in mice and correlate with the severity of malaria in Ugandan children.
- Rabindra K. Mandal
- , Anita Mandal
- & Nathan W. Schmidt
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Article
| Open Access
SARS-CoV-2 infection of human lung epithelial cells induces TMPRSS-mediated acute fibrin deposition
Severe SARS-CoV-2 infection has been associated with extensive diffuse alveolar damage and fibrin formation. Here, Erickson et al describe an infection-induced coagulation mechanism which involves activation of prothrombin by members of TMPRSS genes.
- Rachel Erickson
- , Chang Huang
- & Peter D. Sun
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| Open Access
Creating resistance to avian influenza infection through genome editing of the ANP32 gene family
In chickens, influenza A virus relies on host protein ANP32A. Here the authors use CRISPR/Cas9 to generate homozygous gene edited chickens containing two ANP32A amino acid substitutions that prevent viral polymerase interaction.
- Alewo Idoko-Akoh
- , Daniel H. Goldhill
- & Mike J. McGrew
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| Open Access
HMGB2 regulates the differentiation and stemness of exhausted CD8+ T cells during chronic viral infection and cancer
T cells can become exhausted during chronic virus infection or repeated stimulation by tumour antigens. Here the authors show that High-Mobility Group Box 2 (HMGB2) protein promotes CD8+ T cell memory cell generation in acute viral infection and exhaustion stemness in chronic infection.
- Emily N. Neubert
- , Julia M. DeRogatis
- & Roberto Tinoco
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| Open Access
Identification of potent and selective N-myristoyltransferase inhibitors of Plasmodium vivax liver stage hypnozoites and schizonts
Developing selective N-myristoyltransferase (NMT) inhibitors has been challenging. Here, the authors describe selective NMT inhibitors that can be used as multistage antimalarials, targeting dormant and developing forms of liver and blood stage.
- Diego Rodríguez-Hernández
- , Kamalakannan Vijayan
- & Morten Grøtli
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| Open Access
Neutrophil metalloproteinase driven spleen damage hampers infection control of trypanosomiasis
Trypanosoma brucei infection is characterised by activation of neutrophil associated genes. Here, Pham et al. further dissect the role neutrophils play in tissue pathology, disease outcome and maintenance of adaptive immunity.
- Hien Thi Thu Pham
- , Stefan Magez
- & Magdalena Radwanska
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| Open Access
γδ T cells control murine skin inflammation and subcutaneous adipose wasting during chronic Trypanosoma brucei infection
Trypansome brucei infection can result in colonisation of the skin but how this impacts the skin architecture and immune response has not been fully resolved. Here the authors apply a spatially resolved single cell transcriptomics approach in a murine model of infection, and suggest a role for IL-17- producing γδ T cells in the immune response to T. brucei skin infection.
- Juan F. Quintana
- , Matthew C. Sinton
- & Annette MacLeod
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| Open Access
Persistent symptoms after COVID-19 are not associated with differential SARS-CoV-2 antibody or T cell immunity
Authors utilise a cohort of healthcare workers, infected during the first wave of the SARS-CoV-2 pandemic, to assess symptom persistence and humoral and cellular immunity.
- Daniel M. Altmann
- , Catherine J. Reynolds
- & Rosemary J. Boyton
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| Open Access
Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice
There is a clinical need for effective and efficacious vaccines for Epstein-Barr virus (EBV) that induce substantive and protective immunity. Here the authors use a combined lymph-node targeted adjuvant and subunit vaccine against EBV and show the induction and effectiveness in a human leukocyte antigen expressing murine model.’
- Vijayendra Dasari
- , Lisa K. McNeil
- & Rajiv Khanna
Inflammation and cytomegalovirus viremia during pregnancy drive sex-differentiated differences in mortality and immune development in HIV-exposed infants