The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication DOI Open Access
Paul J. Baker, Andrea C. Bohrer, Ehydel Castro

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 27, 2024

SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known affect disease severity. Yet, how the inflammatory milieu of lung at time exposure impacts control viral replication remains poorly understood. We demonstrate here that immune events in mouse closely preceding significantly impact we identify key innate pathways required limit replication. A diverse set pulmonary stimuli, including resolved antecedent respiratory infections with

Language: Английский

Spatial Transcriptomics: A Powerful Tool in Disease Understanding and Drug Discovery DOI Creative Commons
Junxian Cao, Caifeng Li,

Zhao Cui

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(7), P. 2946 - 2968

Published: Jan. 1, 2024

Recent advancements in modern science have provided robust tools for drug discovery. The rapid development of transcriptome sequencing technologies has given rise to single-cell transcriptomics and single-nucleus transcriptomics, increasing the accuracy accelerating discovery process. With evolution spatial (ST) technology emerged as a derivative approach. Spatial hot topic field omics research recent years; it not only provides information on gene expression levels but also offers expression. This shown tremendous potential disease understanding In this article, we introduce analytical strategies review its applications novel target mechanism unravelling. Moreover, discuss current challenges issues that need be addressed. conclusion, new perspective

Language: Английский

Citations

16

Transforming vaccinology DOI
Rino Rappuoli, Galit Alter, Bali Pulendran

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(19), P. 5171 - 5194

Published: Sept. 1, 2024

Language: Английский

Citations

16

How macrophage heterogeneity affects tuberculosis disease and therapy DOI
David G. Russell, Nelson V. Simwela,

Joshua T. Mattila

et al.

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Language: Английский

Citations

4

High-dose intravenous BCG vaccination induces enhanced immune signaling in the airways DOI Creative Commons
Joshua M. Peters, Edward B. Irvine, Mohau S. Makatsa

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

Intradermal Bacillus Calmette-Guérin (BCG) is the most widely administered vaccine, but it does not sufficiently protect adults against pulmonary tuberculosis. Recent studies in nonhuman primates show that intravenous BCG administration offers superior protection Mycobacterium tuberculosis ( Mtb ). We used single-cell analysis of bronchoalveolar lavage cells from rhesus macaques vaccinated via different routes and doses to identify alterations immune ecosystem airway following vaccination. Our findings reveal high-dose induces an influx polyfunctional T macrophages airways, with alveolar displaying a basal activation state absence purified protein derivative stimulation, defined part by interferon signaling. Enhanced intercellular signaling stronger helper 1–T 17 transcriptional responses were observed stimulation. These results suggest vaccination creates specialized environment primes for effective clearance.

Language: Английский

Citations

2

Engineering customized nanovaccines for enhanced cancer immunotherapy DOI Creative Commons

JinYu Guo,

Changhua Liu, Zhaoyang Qi

et al.

Bioactive Materials, Journal Year: 2024, Volume and Issue: 36, P. 330 - 357

Published: March 11, 2024

Nanovaccines have gathered significant attention for their potential to elicit tumor-specific immunological responses. Despite notable progress in tumor immunotherapy, nanovaccines still encounter considerable challenges such as low delivery efficiency, limited targeting ability, and suboptimal efficacy. With an aim of addressing these issues, engineering customized through modification or functionalization has emerged a promising approach. These tailored not only enhance antigen presentation, but also effectively modulate immunosuppression within the microenvironment. Specifically, they are distinguished by diverse sizes, shapes, charges, structures, unique physicochemical properties, along with ligands. features facilitate lymph node accumulation activation/regulation immune cells. This overview bespoke underscores both prophylactic therapeutic applications, offering insights into future development role cancer immunotherapy.

Language: Английский

Citations

12

Squalene-epoxidase-catalyzed 24(S),25-epoxycholesterol synthesis promotes trained-immunity-mediated antitumor activity DOI Creative Commons
Yongxiang Liu, Zifeng Wang,

Huan Jin

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(4), P. 114094 - 114094

Published: April 1, 2024

The importance of trained immunity in antitumor has been increasingly recognized, but the underlying metabolic regulation mechanisms remain incompletely understood. In this study, we find that squalene epoxidase (SQLE), a key enzyme cholesterol synthesis, is required for β-glucan-induced macrophages and ensuing activity. Unexpectedly, shunt pathway, not classical synthesis catalyzed by SQLE, induction. Specifically, 24(S),25-epoxycholesterol (24(S),25-EC), pathway metabolite, activates liver X receptor increases chromatin accessibility to evoke innate immune memory. Meanwhile, SQLE-induced reactive oxygen species accumulation stabilizes hypoxia-inducible factor 1α protein switching into glycolysis. Hence, our findings identify 24(S),25-EC as metabolite provide important insights how SQLE regulates trained-immunity-mediated

Language: Английский

Citations

8

Trained immunity inducers in cancer immunotherapy DOI Creative Commons
Yongjun Sui, Jay A. Berzofsky

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 16, 2024

While most of the cancer immunotherapy strategies engage adaptive immunity, especially tumor-associated T cells, small fraction responding patients and types cancers amenable, possibility severe adverse effects limit its usage. More effective general interventions are urgently needed. Recently, a de facto innate immune memory, termed ‘trained immunity’, has become new research focal point, promises to be powerful tool for achieving long-term therapeutic benefits against cancers. Trained immunity-inducing agents such as BCG fungal glucan have been shown able avert suppressive tumor microenvironment (TME), enhance cell responses, eventually lead regression. Here, we review current understating trained immunity induction highlight critical roles emergency granulopoiesis, interferon γ tissue-specific induction. Preclinical clinical studies that exploited inducers summarized, repurposed from other fields proposed. We also outline challenges opportunities in future immunotherapies. envisage more vaccines will combine with therapies.

Language: Английский

Citations

8

Novel vaccine strategies to induce respiratory mucosal immunity: advances and implications DOI Creative Commons
Ming Zhou, Haihua Xiao, Xinyi Yang

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(2)

Published: Jan. 16, 2025

Rapid advances in vaccine technology are becoming increasingly important tackling global health crises caused by respiratory virus infections. While traditional vaccines, primarily administered intramuscular injection, have proven effective, they often fail to provide the broad upper tract mucosal immunity, which is urgently needed for first-line control of viral Furthermore, vaccines may not adequately address immune escape emerging variants. In contrast, developed using body's response mechanism can simultaneously establish both systemic and immunity. This dual action effectively allows system function as first line defense, preventing infections at entry points. review highlights efficacy including innovative delivery methods such nasal oral formulations, enhancing local barriers. Notably, offer potential advantages protecting against variants maintaining long-term multidimensional memory tract. addition, a combination largely improves their coverage effectiveness, providing valuable insights future development public inoculation strategies.

Language: Английский

Citations

1

IL-10 suppresses T cell expansion while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus macaques DOI Creative Commons
Christine E Nelson, Christine E Nelson, Christine E Nelson

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(7), P. e1012339 - e1012339

Published: July 1, 2024

The regulation of inflammatory responses and pulmonary disease during SARS-CoV-2 infection is incompletely understood. Here we examine the roles prototypic pro- anti-inflammatory cytokines IFNγ IL-10 using rhesus macaque model mild COVID-19. We find that drives development 18fluorodeoxyglucose (FDG)-avid lesions in lungs as measured by PET/CT imaging but not required for suppression viral replication. In contrast, limits duration acute lesions, serum markers inflammation magnitude virus-specific T cell expansion does impair clearance. also show induces subsequent differentiation effector cells into CD69+CD103+ tissue resident memory (Trm) airways maintains Trm nasal mucosal surfaces, highlighting an unexpected role promoting airway macaques.

Language: Английский

Citations

6

Integrated organ immunity: a path to a universal vaccine DOI
Bali Pulendran

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(2), P. 81 - 82

Published: Jan. 11, 2024

Language: Английский

Citations

5