Enhanced tuberculosis control via leveraging dendritic cell-mediated Th1 responses in preventive and immunotherapeutic vaccine strategies.

Introduction: Insufficient vaccine efficacy of the Bacillus Calmette-Guérin (BCG) and long, expensive tuberculosis (TB) treatments highlight the need for better TB control measures.

Methods: This study evaluated whether the adoptive transfer of dendritic cell (DC)-based vaccines pulsed with culture filtrate antigens (CFA) of Mycobacterium tuberculosis (Mtb) could enhance BCG efficacy and support anti-TB drug therapy.

Results: In BCG-vaccinated mice, adoptive transfer of CFA-pulsed DCs promoted swift T cell recruitment to the lung parenchyma, reducing bacterial load within 1 week post-infection, promoting the generation of tissue-resident T cells and expansion of CD4 T cells co-producing IFN-γ, IL-2, and/or TNF-α.

Adjunctive beneficial effect of c-di-GMP, a STING agonist, in enhancing protective efficacy of TLR4-adjuvanted tuberculosis subunit vaccine formulations.

Background: Effective subunit vaccine development requires selecting appropriate adjuvant formulations to trigger desired adaptive immune responses. This study explores the immunogenicity and tuberculosis (TB) vaccine potential of antigens (Ags) combined with Toll-like receptor 4 (TLR4) adjuvants and a stimulator of interferon genes (STING) agonist.

Methods: In this work, we investigated the combination of Ags with TLR4 adjuvants (monophosphoryl lipid A / dimethyldioctadecylammonium bromide; MPL/DDA or glucopyranosyl lipid adjuvant-stable emulsion; GLA-SE) and a STING agonist, c-di-GMP (CDG).

Geometric Adjustment of T Cell-Sensitive Nanorobots for Enhanced Stability.

Personalized dendritic cell (DC) based vaccines offer promising immunotherapeutic approaches for cancers and infectious diseases by leveraging living DCs to stimulate a patient's immune system through interactions with T cells. However, conventional DC-based vaccines face significant challenges, including limited stability and short storage lifespan of the living cells. To overcome these limitations, smart artificial nanorobots, termed nano-bone marrow dendritic cell (BMDC)-originated T cell activators (nano-BOTs) are developed by incorporating 1-dimensional (1D) nanoparticles to enhance stability and activation efficacy.

Antigen Cross-Presentation by Type-2 Innate Lymphoid Cells Facilitates the Activation of Antitumor CD8+ T Cells.

Unlabelled: Type-2 innate lymphoid cells (ILC2) exhibit dual functions in cancer, both promoting and inhibiting tumor growth by regulating antitumor immune responses. Elucidation of the precise mechanisms by which ILCs regulate adaptive immune responses could support the development of improved immunotherapeutic approaches. In this study, we revealed that ILC2s possess the capacity to internalize, process, and present exogenous tumor antigen on MHC-I molecules, along with costimulatory molecules, to CD8+ T cells, thereby inducing their differentiation into CTLs.

A temperature-responsive PLA-based nanosponge as a novel nanoadjuvant and efficient delivery carrier of Ag85B for effective vaccine against Mycobacterium tuberculosis.

Background: Tuberculosis (TB) is a contagious disease and the second leading cause of death worldwide. The Bacille Calmette-Guérin (BCG) vaccine, the only licensed TB vaccine, has insufficient protective efficacy in adults, necessitating the development of new TB vaccines. Ag85B, a protein-subunit TB vaccine, is a promising candidate due to its high immunogenicity.

Immunogenicity and protective efficacy of a multi-antigenic adenovirus-based vaccine candidate against .

Introduction: The inadequate efficacy of the Bacillus Calmette-Guérin (BCG) vaccine against adult pulmonary tuberculosis (TB) necessitates the development of new and effective vaccines. Human adenovirus serotype 5 (Ad5), which induces T-cell response, is a widely used viral vector. In this study, we aimed to evaluate the efficacy of a multi-antigenic recombinant Ad5 vectored vaccine and determine the optimal immunization route for enhanced immune response against .

Noncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis.

Until now, Hippo pathway-mediated nucleocytoplasmic translocation has been considered the primary mechanism by which yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional coactivators regulate cell proliferation and differentiation via transcriptional enhanced associate domain (TEAD)-mediated target gene expression. In this study, however, we found that TAZ, but not YAP, is associated with the Golgi apparatus in macrophages activated via Toll-like receptor ligands during the resolution phase of inflammation. Golgi-associated TAZ enhanced vesicle trafficking and secretion of proinflammatory cytokines in M1 macrophage independent of the Hippo pathway.

A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy.

Immune checkpoint blockade (ICB) has become a standard anti-cancer treatment, offering durable clinical benefits. However, the limited response rate of ICB necessitates biomarkers to predict and modulate the efficacy of the therapy. The gut microbiome's influence on ICB efficacy is of particular interest due to its modifiability through various interventions.

analysis for the development of multi-epitope vaccines against .

As Bacille Calmette-Guérin (BCG) vaccine's effectiveness is limited to only children, the development of new tuberculosis (TB) vaccines is being studied using several platforms, and a novel TB vaccine that overcomes this limitation is required. In this study, we designed an effective multi-epitope vaccine against using immunoinformatic analysis. First, we selected 11 highly antigenic proteins based on previous research: Ag85A, Ag85B, Ag85C, ESAT-6, MPT64, Rv2660c, TB10.

MRGM: an enhanced catalog of mouse gut microbial genomes substantially broadening taxonomic and functional landscapes.

Mouse gut microbiome research is pivotal for understanding the human gut microbiome, providing insights into disease modeling, host-microbe interactions, and the dietary influence on the gut microbiome. To enhance the translational value of mouse gut microbiome studies, we need detailed and high-quality catalogs of mouse gut microbial genomes. We introduce the Mouse Reference Gut Microbiome (MRGM), a comprehensive catalog with 42,245 non-redundant mouse gut bacterial genomes across 1,524 species.

Harnessing IL-2 for immunotherapy against cancer and chronic infection: a historical perspective and emerging trends.

IL-2 therapy, which enhances the function of CD8 + T cells, was initially employed as the cornerstone of immunotherapy against cancer. However, the impact of this therapy extends beyond CD8 + T cells to cells expressing IL-2R, such as endothelial cells and regulatory T cells (Tregs), resulting in various side effects. Consequently, IL-2 therapy has taken a step back from the forefront of treatment.

MRGM: An enhanced catalog of mouse gut microbial genomes substantially broadening taxonomic and functional landscapes.

Mouse gut microbiome research is pivotal for understanding the human gut microbiome, providing insights into disease modeling, host-microbe interactions, and the dietary influence on the gut microbiome. To enhance the translational value of mouse gut microbiome studies, we need detailed and high-quality catalogs of mouse gut microbial genomes. We introduce the Mouse Reference Gut Microbiome (MRGM), a comprehensive catalog with 42,245 non-redundant mouse gut bacterial genomes across 1,524 species.

Tumor phagocytosis-driven STING activation invigorates antitumor immunity and reprograms the tumor micro-environment.

Immunogenic cell death (ICD) holds the potential for in situ tumor vaccination while concurrently eradicating tumors and stimulating adaptive immunity. Most ICD inducers, however, elicit insufficient immune responses due to negative feedback against ICD biomarkers, limited infiltration of antitumoral immune cells, and the immunosuppressive tumor micro-environment (TME). Recent findings highlight the pivotal roles of stimulators of interferon gene (STING) activation, particularly in stimulating antigen-presenting cells (APCs) and TME reprogramming, addressing ICD limitations.

A novel small molecule, CU05-1189, targeting the pleckstrin homology domain of PDK1 suppresses VEGF-mediated angiogenesis and tumor growth by blocking the Akt signaling pathway.

Inhibition of angiogenesis is considered a promising therapeutic approach for cancer treatment. Our previous genetic research showed that the use of a cell-penetrating peptide to inhibit the pleckstrin homology (PH) domain of 3-phosphoinositide-dependent kinase 1 (PDK1) was a viable approach to suppress pathological angiogenesis. Herein, we synthesized and characterized a novel small molecule, CU05-1189, based on our prior study and present evidence for the first time that this compound possesses antiangiogenic properties both and .

A virtual memory CD8 T cell-originated subset causes alopecia areata through innate-like cytotoxicity.

Virtual memory T (T) cells are a T cell subtype with a memory phenotype but no prior exposure to foreign antigen. Although T cells have antiviral and antibacterial functions, whether these cells can be pathogenic effectors of inflammatory disease is unclear. Here we identified a T cell-originated CD44CD49d CD8 T cell subset with features of tissue residency.

Discovery of highly immunogenic spleen-resident FCGR3CD103 cDC1s differentiated by IL-33-primed ST2 basophils.

Recombinant interleukin-33 (IL-33) inhibits tumor growth, but the detailed immunological mechanism is still unknown. IL-33-mediated tumor suppression did not occur in Batf3 mice, indicating that conventional type 1 dendritic cells (cDC1s) play a key role in IL-33-mediated antitumor immunity. A population of CD103 cDC1s, which were barely detectable in the spleens of normal mice, increased significantly in the spleens of IL-33-treated mice.

Protective Efficacy and Immunogenicity of Rv0351/Rv3628 Subunit Vaccine Formulated in Different Adjuvants Against Infection.

Bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine for tuberculosis (TB) prevention. Previously, our group demonstrated the vaccine potential of Rv0351 and Rv3628 against (Mtb) infection by directing Th1-biased CD4 T cells co-expressing IFN-γ, TNF-α, and IL-2 in the lungs. Here, we assessed immunogenicity and vaccine potential of the combined Ags (Rv0351/Rv3628) formulated in different adjuvants as subunit booster in BCG-primed mice against hypervirulent clinical Mtb strain K (Mtb K).

Deletion of PD-1 destabilizes the lineage identity and metabolic fitness of tumor-infiltrating regulatory T cells.

Regulatory T (T) cells have an immunosuppressive function and highly express the immune checkpoint receptor PD-1 in the tumor microenvironment; however, the function of PD-1 in tumor-infiltrating (TI) T cells remains controversial. Here, we showed that conditional deletion of PD-1 in T cells delayed tumor progression. In Pdcd1Foxp3 mice, in which both PD-1-expressing and PD-1-deficient T cells coexisted in the same tissue environment, conditional deletion of PD-1 in T cells resulted in impairment of the proliferative and suppressive capacity of TI T cells.