Destabilisation of T cell-dependent humoral immunity in sepsis

Clinical Science, Journal Year: 2024, Volume and Issue: 138(1), P. 65 - 85

Published: Jan. 1, 2024

Abstract Sepsis is a heterogeneous condition defined as life-threatening organ dysfunction caused by dysregulated host response to infection. For some, sepsis presents predominantly suppressive disorder, whilst others experience pro-inflammatory which can culminate in ‘cytokine storm’. Frequently, patients signs of concurrent hyper-inflammation and immunosuppression, underpinning the difficulty directing effective treatment. Although intensive care unit mortality rates have improved recent years, one-third discharged die within following year. Half post-sepsis deaths are due exacerbation pre-existing conditions, half complications arising from deteriorated immune system. It has been suggested that intense infection may induce irreversible metabolic reprogramming cells. As critical arm protection vertebrates, alterations adaptive system devastating repercussions. Indeed, marked depletion lymphocytes observed sepsis, correlating with increased mortality. Such sepsis-induced lymphopenia profound consequences on how T cells respond but equally humoral both elicited B supported distinct CD4+ follicular helper (TFH) cell subsets. The immunosuppressive state further exacerbated functional impairments remaining lymphocyte population, including presence expressing dysfunctional or exhausted phenotypes. This review will specifically focus destabilises system, closer examination TFH affected corresponding impact immunity.

Language: Английский

---

Unconventional T cells and kidney disease

Nature Reviews Nephrology, Journal Year: 2021, Volume and Issue: 17(12), P. 795 - 813

Published: Aug. 26, 2021

Language: Английский

---

Intestinal changes and immune responses during Clostridium perfringens-induced necrotic enteritis in broiler chickens

Poultry Science, Journal Year: 2021, Volume and Issue: 101(3), P. 101652 - 101652

Published: Dec. 7, 2021

Clostridium perfringens-induced necrotic enteritis (NE) is an economically important disease of broiler chickens. The present study evaluated the effect C. perfringens on intestinal histomorphometry, enteric microbial colonization, and host immune responses using 3 experimental NE reproduction methods. groups consisted 1) unchallenged Control diet (corn-soybean meal), 2) + Eimera inoculation at d 11 followed by challenge 15 (ECp), 3) Wheat-based (WCp), 4) Eimeria (WECp). results showed that chickens receiving ECp WECp had reduced (P < 0.05) bird performance coupled with gross lesions epithelial damage 17 24 age compared to control birds. These administered birds also increased ileal colonization clostridia E. coli 24, while resident Lactobacillus counts were age. Furthermore, jejunal transcription IL-6, IL-10, annexin-A1 IL-2 genes was upregulated in group, whereas TNF receptor associated factor (TRAF)-3 gene treated when group. Additionally, stimulation chicken splenocytes cecal tonsilocytes virulent bacilli or their secretory proteins resulted a higher frequency T cells upregulation MHC-II molecule, as determined flow cytometry. findings suggest perfringens, inducing changes microbiota, can trigger responses. methods coccidia without wheat-based dietary predisposition seem facilitate optimal thus, may provide better avenues for future research.

Language: Английский

---

Immunostimulatory DNA Hydrogel Enhances Protective Efficacy of Nanotoxoids against Bacterial Infection

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(31)

Published: April 25, 2023

Abstract While vaccines have been highly successful in protecting against various infections, there are still many high‐priority pathogens for which no clinically approved formulations. To overcome this challenge, researchers explored the use of nanoparticulate strategies more effective antigen delivery to immune system. Along these lines, nanotoxoids a promising biomimetic platform that leverages cell membrane coating technology safely deliver otherwise toxic bacterial antigens their native form antivirulence vaccination. Here, order further boost immunogenicity, formulated staphylococcal α ‐hemolysin embedded into DNA‐based hydrogel with immunostimulatory CpG motifs. The resulting nanoparticle–hydrogel composite is injectable and improves vivo vaccine while simultaneously stimulating nearby cells. This leads elevated antibody production stronger antigen‐specific cellular responses. In murine models pneumonia skin infection caused by methicillin‐resistant Staphylococcus aureus , mice vaccinated hybrid formulation well‐protected. work highlights benefits combining systems hydrogels single platform, approach can be readily generalized wide range infectious diseases.

Language: Английский

---

Designing Multi-Antigen Vaccines Against Acinetobacter baumannii Using Systemic Approaches

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: April 16, 2021

Vaccines and monoclonal antibodies are promising approaches for preventing treating infections caused by multidrug resistant Acinetobacter baumannii . However, only partial protection has been achieved with many previously tested protein antigens, which suggests that vaccines incorporating multiple antigens may be necessary in order to obtain high levels of protection. Several aspects use the wealth omic data available A. have not fully exploited antigen identification. In this study, fractionated proteomic computational from ~4,200 genomes increased number proteins potentially accessible humoral response 8,824 non-redundant panproteome. Among them, 59% carried predicted B-cell epitopes T-cell recognized two or more alleles HLA class II DP supertype. Potential cross-reactivity human was detected 8.9% at level 2.7% epitope level. Individual were associated different infection types genomic, transcriptomic functional analyses. High intra-clonal genome density permitted identification international clone as a “vaccitype”, 20% identified specific clone. Network-based centrality measurements used identify immunologic nodes. Data formatted, unified stored warehouse database, subsequently synergistic combinations vaccination strategies. This study supports idea integration multi-omic fundamental knowledge pathobiology drug-resistant bacteria can facilitate development effective multi-antigen against these challenging infections.

Language: Английский

---

Don’t Let It Get Under Your Skin! – Vaccination Protects the Skin Barrier of Common Carp From Disruption Caused by Cyprinid Herpesvirus 3

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Jan. 31, 2022

Vaccination is the best form of protecting fish against viral diseases when pathogen cannot be contained by biosecurity measures. Vaccines based on live attenuated viruses seem to most effective for vaccination challenging pathogens like Cyprinid herpesvirus 3 . However, there are still knowledge gaps how these vaccines effectively protect from deadly disease caused epitheliotropic CyHV-3, and which aspects non-direct protection skin or gill integrity function important in aquatic environment. To elucidate some elements protection, common carp were vaccinated CyHV-3 using a double deletion vaccine virus KHV-T ΔDUT/TK absence presence mix beta-defensins 1, 2 as adjuvants. induced marginal clinical signs, low load minor upregulation cd4 , cd8 igm gene expression fish, while neutralisation activity blood serum rose 14 days post (dpv). A challenge infection with severe 80-100% mortality non-vaccinated carp, no was recorded &gt;1,000-fold lower skin, kidney. Histological analysis showed strongest pathological changes complete destruction epidermis carp. In T B cell responses severely downregulated, inflammation stress increased upon challenge, whereas had boosted neutrophil, responses. disruption barrier (tight adherence junction, desmosomes, mucins) led an uncontrolled increase bacteria likely exacerbated pathology. Using vaccine, we able show that provide lead preservation integrity, supports successful additional environment foster development

Language: Английский

---

Heterologous Immunity Between SARS-CoV-2 and Pathogenic Bacteria

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Jan. 27, 2022

Heterologous immunity, when the memory T cell response elicited by one pathogen recognizes another pathogen, has been offered as a contributing factor for high variability in coronavirus disease 2019 (COVID-19) severity outcomes. Here we demonstrate that sensitization with bacterial peptides can induce heterologous immunity to severe acute respiratory syndrome 2 (SARS-CoV-2) derived and vaccination SARS-CoV-2 spike protein peptides. Using silico prediction methods, identified 6 sequence homology either or non-structural 3 (NSP3) of SARS-CoV-2. Notwithstanding effects bystander activation, vitro co-cultures showed all individuals tested ( n =18) developed sensitized recall responses measured included cytokine production (IFN-γ, TNF, IL-2), activation (CD69) proliferation (CellTrace). As an extension principle between pathogens COVID-19, tracked donor before after cross-reactive similar protein. We found could These findings provide mechanism common SARS-CoV-2, which may explain variance COVID-19 outcomes from asymptomatic severe. also proof-of-concept pathogenic bacteria

Language: Английский

---

In vitro evaluation of immune responses to bacterial hydrogels for the development of living therapeutic materials

Biomaterials Advances, Journal Year: 2023, Volume and Issue: 153, P. 213554 - 213554

Published: July 13, 2023

Language: Английский

---

T cell reactivity to Bordetella pertussis is highly diverse regardless of childhood vaccination

Cell Host & Microbe, Journal Year: 2023, Volume and Issue: 31(8), P. 1404 - 1416.e4

Published: July 24, 2023

Language: Английский

---

A Key Role of CD8+ T Cells in Controlling of Tuberculosis Infection

Diagnostics, Journal Year: 2023, Volume and Issue: 13(18), P. 2961 - 2961

Published: Sept. 15, 2023

The main role in the control of tuberculosis infection is played by macrophages and Th1 CD8+ T cells. study aimed to identify most diagnostically significant cell subsets patients. Methods: Peripheral blood samples from patients with clinical, radiological, bacteriologically confirmed pulmonary (TB, n = 32) healthy subjects (HC, 31) were collected analyzed using 10-color flow cytometry. Results: frequency EM4 CD3+CD8+ cells was reduced peripheral tuberculosis, while relative absolute number EM1 increased compared group. CD57 expression on EM1, EM2, pE1 cells, whereas EM3 had a high level expression. Tc2 (CCR6–CXCR3–) increased, Tc1 (CCR6–CXCR3+) decreased, donors. Conclusions: Patients have an abnormal profile demonstrate their impaired maturation functional activity.

Language: Английский

---