A guide to complement biology, pathology and therapeutic opportunity

Nature reviews. Immunology, Год журнала: 2023, Номер 24(2), С. 118 - 141

Опубликована: Сен. 5, 2023

Язык: Английский

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Recent advances and evolving concepts in Still’s disease

Nature Reviews Rheumatology, Год журнала: 2024, Номер 20(2), С. 116 - 132

Опубликована: Янв. 11, 2024

Язык: Английский

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Impact of Environmental Factors on Hypertension and Associated Cardiovascular Disease

Canadian Journal of Cardiology, Год журнала: 2023, Номер 39(9), С. 1229 - 1243

Опубликована: Июль 6, 2023

Язык: Английский

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Macrophage phagocytosis of SARS-CoV-2-infected cells mediates potent plasmacytoid dendritic cell activation

Cellular and Molecular Immunology, Год журнала: 2023, Номер 20(7), С. 835 - 849

Опубликована: Май 30, 2023

Abstract Early and strong interferon type I (IFN-I) responses are usually associated with mild COVID-19 disease, whereas persistent or unregulated proinflammatory cytokine severe disease outcomes. Previous work suggested that monocyte-derived macrophages (MDMs) resistant unresponsive to SARS-CoV-2 infection. Here, we demonstrate upon phagocytosis of SARS-CoV-2-infected cells, MDMs activated secrete IL-6 TNF. Importantly, in turn mediate activation plasmacytoid dendritic cells (pDCs), leading the secretion high levels IFN-α Furthermore, pDC promoted production by MDMs. This kind was dependent on direct integrin-mediated cell‒cell contacts involved stimulation TLR7 STING signaling pathways. Overall, present study describes a novel potent pathway is linked macrophage-mediated clearance infected cells. These findings suggest infection rate may lead exaggerated responses, which contribute tissue damage disease.

Язык: Английский

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The complement alternative pathway in paroxysmal nocturnal hemoglobinuria: From a pathogenic mechanism to a therapeutic target

Immunological Reviews, Год журнала: 2022, Номер 313(1), С. 262 - 278

Опубликована: Сен. 15, 2022

Summary Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal, not malignant, hematological disease characterized by intravascular hemolysis, thrombophilia and bone marrow failure. While this latter presentation due to T‐cell mediated auto‐immune disorder resembling acquired aplastic anemia, the first two clinical presentations are largely driven complement pathway. Indeed, PNH broad impairment of regulation on affected cells, which lack regulators CD55 CD59. The deficiency these proteins from blood cells somatic mutation in phosphatidylinositol N‐acetylglucosaminyltransferase subunit A gene causing disease, impairs surface expression all linked via glycosylphosphatidylinositol anchor. CD59 erythrocytes accounts for hallmark PNH, chronic, complement‐mediated hemolysis. This hemolysis results impaired alternative pathway upstream cascade, as well downstream terminal represented indication development anti‐complement agents, therapeutic interception cascade at level C5 led remarkable changes natural history disease. Nevertheless, use an inhibitor highlighted broader derangement shedding light pivotal role Here we review current understanding including emergence C3‐mediated extravascular patients anti‐C5 therapies. These observations provide rationale novel inhibitors treatment PNH. Recent preclinical data proximal intercepting with aim improving discussed, together their implications animating lively debate scientific community.

Язык: Английский

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Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

ABSTRACT In a subset of SARS-CoV-2-infected individuals treated with the antiviral nirmatrelvir-ritonavir, virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used mathematical model to describe longitudinal viral load dynamics 51 20 whom rebounded. Target cell preservation, either by robust innate immune response or initiation N-R near time symptom onset, coupled incomplete clearance, appears be main factor leading rebound. Moreover, occurrence is likely influenced treatment relative progression infection, earlier treatments higher chance A comparison an untreated cohort suggests that early nirmatrelvir-ritonavir may associated delay in onset adaptive response. Nevertheless, our demonstrates extending course 10-day regimen greatly diminish people mild-to-moderate COVID-19 and who at high risk severe disease. Altogether, results suggest some individuals, standard 5-day starting around completely eliminate virus. Thus, after ends, can if effective has fully developed. These findings on role target preservation clearance also offer possible explanation for other SARS-CoV-2. IMPORTANCE Nirmatrelvir-ritonavir initial reduction followed once stopped. show timing influence stops growth preserves cells but lead full adequately developed, remaining Our provide insights into help develop better strategies minimize possibility.

Язык: Английский

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Biological effects of COVID-19 on lung cancer: Can we drive our decisions

Frontiers in Oncology, Год журнала: 2022, Номер 12

Опубликована: Окт. 10, 2022

COVID-19 infection caused by SARS-CoV-2 is considered catastrophic because it affects multiple organs, particularly those of the respiratory tract. Although consequences this are not fully clear, causes damage to lungs, cardiovascular and nervous systems, other subsequently inducing organ failure. In particular, effects SARS-CoV-2-induced inflammation on cancer cells tumor microenvironment need be investigated. may alter microenvironment, promoting cell proliferation dormant (DCC) reawakening. DCCs reawakened upon with can populate premetastatic niche in lungs leading dissemination. DCC reawakening consequent neutrophil monocyte/macrophage activation an uncontrolled cascade pro-inflammatory cytokines most severe clinical COVID-19. Moreover, extracellular traps have been demonstrated activate dissemination into lungs. Further studies warranted better define roles as well development metastasis; results these will aid further targeted therapies, both for prevention treatment patients

Язык: Английский

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Natural killer cell responses during SARS-CoV-2 infection and vaccination in people living with HIV-1

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Ноя. 3, 2023

Abstract Natural killer (NK) cell subsets with adaptive properties are emerging as regulators of vaccine-induced T and B responses specialized towards antibody-dependent functions contributing to SARS-CoV-2 control. Although HIV-1 infection is known affect the NK pool, additional impact and/or vaccination on in people living HIV (PLWH) has remained unexplored. Our data show that skews cells a more differentiated/adaptive CD57 + FcεRIγ − phenotype PLWH. A similar subset was induced following naïve PLWH addition CD56 bright population cytotoxic potential. Antibody-dependent function showed robust durable Spike up 148 days post-infection, enriched cells. were further boosted by first vaccine dose exposed individuals peaked after second The presence associated magnitude cellular humoral responses. These suggest features can be effectively engaged complement boost immunity potentially vulnerable groups such

Язык: Английский

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Characteristics of lymphocyte subset alterations in COVID-19 patients with different levels of disease severity

Virology Journal, Год журнала: 2022, Номер 19(1)

Опубликована: Ноя. 19, 2022

Abstract Background Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by severe acute syndrome coronavirus 2 (SARS-CoV-2), which had rapidly spread all over the world and public health emergencies in past two years. Although diagnosis treatment for COVID-19 have been well defined, immune cell characteristics key lymphocytes subset alterations patients not thoroughly investigated. Methods The levels of cells including T cells, B natural killer (NK) 548 hospitalized patients, 30 types lymphocyte subsets 125 admitted to Wuhan Huoshenshan Hospital China were measured using flow cytometry. relationship between with cytokine interleukin-6 (IL-6) single-cell RNA sequencing (scRNA-seq) data obtained from peripheral blood mononuclear (PBMCs) also analysed patients. Results In this study, we found that critical infection exhibited an overall decline CD4 + CD8 total NK compared mild However, number subsets, such as CD21 low CD38 effector T4 PD1 depleted T8 was moderately increased cases. Notably, except memory plasma blasts Tregs, markedly decreased IL-6 30-fold higher than those healthy Moreover, scRNA-seq showed obvious differences distribution numbers persons, subsets-specific marker genes CD4, CD19, CCR7, IL7R, Conclusion A comprehensive decrease clear association clinical characteristics.

Язык: Английский

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SARS-CoV-2 epitopes inform future vaccination strategies

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Ноя. 25, 2022

All currently approved COVID-19 vaccines utilize the spike protein as their immunogen. SARS-CoV-2 variants of concern (VOCs) contain mutations in protein, enabling them to escape infection- and vaccination-induced immune responses cause reinfection. New are hence being researched intensively. Studying epitopes is essential for vaccine design, identifying targets broadly neutralizing antibody immunodominant T-cell reveal candidates inclusion next-generation vaccines. We summarize major studies which have reported on thus far. These results suggest that a future pan-coronavirus vaccines, not only protect against but numerous other coronaviruses, may be possible. The gotten less attention than provide new strategies control infection. T-cells target many antigens spike, recognizing within these antigens, thereby limiting chance by VOCs mainly possess mutations. Therefore, augmenting adequate protection despite broad VOCs.

Язык: Английский

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