| 1. |
- Manry, Jérémy, et al.
(författare)
-
The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
- 2022
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21
-
Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
|
|
| 2. |
- Bastard, Paul, et al.
(författare)
-
Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1.
- 2021
-
Ingår i: The Journal of experimental medicine. - 1540-9538. ; 218:7
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
|
|
| 3. |
- Lévy, Romain, et al.
(författare)
-
Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency.
- 2023
-
Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 220:2
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with inherited CARMIL2 or CD28 deficiency have defective T cell CD28 signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three CARMIL2 isoforms is produced and functional across leukocyte subsets. Tested mutant CARMIL2 alleles from 89 patients and 52 families impair canonical NF-κB but not AP-1 and NFAT activation in T cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient patients display recalcitrant warts and low blood counts of CD4+ and CD8+ memory T cells and CD4+ TREGs. Unlike CD28-deficient patients, they have low counts of NK cells and memory B cells, and their antibody responses are weak. CARMIL2 deficiency is fully penetrant by the age of 10 yr and is characterized by numerous infections, EBV+ smooth muscle tumors, and mucocutaneous inflammation, including inflammatory bowel disease. Patients with somatic reversions of a mutant allele in CD4+ T cells have milder phenotypes. Our study suggests that CARMIL2 governs immunological pathways beyond CD28.
|
|
| 4. |
- Graham, Emily B., et al.
(författare)
-
Microbes as Engines of Ecosystem Function : When Does Community Structure Enhance Predictions of Ecosystem Processes?
- 2016
-
Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Microorganisms are vital in mediating the earth's biogeochemical cycles; yet, despite our rapidly increasing ability to explore complex environmental microbial communities, the relationship between microbial community structure and ecosystem processes remains poorly understood. Here, we address a fundamental and unanswered question in microbial ecology: 'When do we need to understand microbial community structure to accurately predict function?' We present a statistical analysis investigating the value of environmental data and microbial community structure independently and in combination for explaining rates of carbon and nitrogen cycling processes within 82 global datasets. Environmental variables were the strongest predictors of process rates but left 44% of variation unexplained on average, suggesting the potential for microbial data to increase model accuracy. Although only 29% of our datasets were significantly improved by adding information on microbial community structure, we observed improvement in models of processes mediated by narrow phylogenetic guilds via functional gene data, and conversely, improvement in models of facultative microbial processes via community diversity metrics. Our results also suggest that microbial diversity can strengthen predictions of respiration rates beyond microbial biomass parameters, as 53% of models were improved by incorporating both sets of predictors compared to 35% by microbial biomass alone. Our analysis represents the first comprehensive analysis of research examining links between microbial community structure and ecosystem function. Taken together, our results indicate that a greater understanding of microbial communities informed by ecological principles may enhance our ability to predict ecosystem process rates relative to assessments based on environmental variables and microbial physiology.
|
|
| 5. |
- Krause, Sascha, et al.
(författare)
-
Trait-based approaches for understanding microbial biodiversity and ecosystem functioning
- 2014
-
Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 5, s. 251-
-
Forskningsöversikt (refereegranskat)abstract
- In ecology, biodiversity-ecosystem functioning (BEE) research has seen a shift in perspective from taxonomy to function in the last two decades, with successful application of trait-based approaches. This shift offers opportunities for a deeper mechanistic understanding of the role of biodiversity in maintaining multiple ecosystem processes and services. In this paper, we highlight studies that have focused on BEE of microbial communities with an emphasis on integrating trait-based approaches to microbial ecology. In doing so, we explore some of the inherent challenges and opportunities of understanding BEE using microbial systems. For example, microbial biologists characterize communities using gene phylogenies that are often unable to resolve functional traits. Additionally, experimental designs of existing microbial BEE studies are often inadequate to unravel BEE relationships. We argue that combining eco-physiological studies with contemporary molecular tools in a trait-based framework can reinforce our ability to link microbial diversity to ecosystem processes. We conclude that such trait-based approaches are a promising framework to increase the understanding of microbial BEE relationships and thus generating systematic principles in microbial ecology and more generally ecology.
|
|
| 6. |
- Philippot, Laurent, et al.
(författare)
-
Microbial Community Resilience across Ecosystems and Multiple Disturbances
- 2021
-
Ingår i: Microbiology and molecular biology reviews. - : American Society for Microbiology. - 1092-2172 .- 1098-5557. ; 85:2
-
Forskningsöversikt (refereegranskat)abstract
- The ability of ecosystems to withstand disturbances and maintain their functions is being increasingly tested as rates of change intensify due to climate change and other human activities. Microorganisms are crucial players underpinning ecosystem functions, and the recovery of microbial communities from disturbances is therefore a key part of the complex processes determining the fate of ecosystem functioning. However, despite global environmental change consisting of numerous pressures, it is unclear and controversial how multiple disturbances affect microbial community stability and what consequences this has for ecosystem functions. This is particularly the case for those multiple or compounded disturbances that occur more frequently than the normal recovery time. The aim of this review is to provide an overview of the mechanisms that can govern the responses of microbes to multiple disturbances across aquatic and terrestrial ecosystems. We first summarize and discuss properties and mechanisms that influence resilience in aquatic and soil biomes to determine whether there are generally applicable principles. Following, we focus on interactions resulting from inherent characteristics of compounded disturbances, such as the nature of the disturbance, timing, and chronology that can lead to complex and nonadditive effects that are modulating the response of microorganisms.
|
|
| 7. |
- Philippot, Laurent, et al.
(författare)
-
The ecological coherence of high bacterial taxonomic ranks
- 2010
-
Ingår i: Nature Reviews Microbiology. - : Springer Science and Business Media LLC. - 1740-1526 .- 1740-1534. ; 8:7, s. 523-529
-
Forskningsöversikt (refereegranskat)abstract
- The species is a fundamental unit of biological organization, but its relevance for Bacteria and Archaea is still hotly debated. Even more controversial is whether the deeper branches of the ribosomal RNA-derived phylogenetic tree, such as the phyla, have ecological importance. Here, we discuss the ecological coherence of high bacterial taxa in the light of genome analyses and present examples of niche differentiation between deeply diverging groups in terrestrial and aquatic systems. The ecological relevance of high bacterial taxa has implications for bacterial taxonomy, evolution and ecology.
|
|
| 8. |
- Wessén, Ella, et al.
(författare)
-
Spatial distribution of ammonia-oxidizing bacteria and archaea across a 44-hectare farm related to ecosystem functioning
- 2011
-
Ingår i: Isme Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 5:7, s. 1213-1225
-
Tidskriftsartikel (refereegranskat)abstract
- Characterization of spatial patterns of functional microbial communities could facilitate the understanding of the relationships between the ecology of microbial communities, the biogeochemical processes they perform and the corresponding ecosystem functions. Because of the important role the ammonia-oxidizing bacteria (AOB) and archaea (AOA) have in nitrogen cycling and nitrate leaching, we explored the spatial distribution of their activity, abundance and community composition across a 44-ha large farm divided into an organic and an integrated farming system. The spatial patterns were mapped by geostatistical modeling and correlations to soil properties and ecosystem functioning in terms of nitrate leaching were determined. All measured community components for both AOB and AOA exhibited spatial patterns at the hectare scale. The patchy patterns of community structures did not reflect the farming systems, but the AOB community was weakly related to differences in soil pH and moisture, whereas the AOA community to differences in soil pH and clay content. Soil properties related differently to the size of the communities, with soil organic carbon and total nitrogen correlating positively to AOB abundance, while clay content and pH showed a negative correlation to AOA abundance. Contrasting spatial patterns were observed for the abundance distributions of the two groups indicating that the AOB and AOA may occupy different niches in agro-ecosystems. In addition, the two communities correlated differently to community and ecosystem functions. Our results suggest that the AOA, not the AOB, were contributing to nitrate leaching at the site by providing substrate for the nitrite oxidizers. The ISME Journal (2011) 5, 1213-1225; doi:10.1038/ismej.2010.206; published online 13 January 2011 Subject Category: microbial ecology and functional diversity of natural habitats
|
|
| 9. |
- Zhang, Q, et al.
(författare)
-
Autoantibodies against type I IFNs in patients with critical influenza pneumonia
- 2022
-
Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 219:11
-
Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6–73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients’ autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients <70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10−5), but not >70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10−5), especially those <70 yr old (OR = 139.9, P = 3.1 × 10−10). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for ∼5% of cases of life-threatening influenza pneumonia in patients <70 yr old.
|
|
