Gut microbiota: a crucial player in the combat against tuberculosis DOI Creative Commons
Lin Jie, Dongli Chen,

Yonghao Yan

et al.

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

Published: Oct. 22, 2024

The mammalian gastrointestinal tract quickly becomes densely populated with foreign microorganisms shortly after birth, thereby establishing a lifelong presence of microbial community. These commensal gut microbiota serve various functions, such as providing nutrients, processing ingested compounds, maintaining homeostasis, and shaping the intestinal structure in host. Dysbiosis, which is characterized by an imbalance community, closely linked to numerous human ailments has recently emerged key factor health prognosis. Tuberculosis (TB), highly contagious potentially fatal disease, presents pressing need for improved methods prevention, diagnosis, treatment strategies. Thus, we aim explore latest developments on how host’s immune defenses, inflammatory responses, metabolic pathways, nutritional status collectively impact susceptibility or resilience against Mycobacterium tuberculosis infection. review addresses fluctuations not only affect equilibrium these physiological processes but also indirectly influence capacity resist M. . This work highlights central role host–microbe interactions provides novel insights advancement preventative therapeutic approaches tuberculosis.

Language: Английский

BCG immunization induces CX3CR1hi effector memory T cells to provide cross-protection via IFN-γ-mediated trained immunity DOI
Kim A. Tran, Erwan Pernet, Mina Sadeghi

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(3), P. 418 - 431

Published: Jan. 15, 2024

Language: Английский

Citations

32
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
Intravenous BCG-mediated protection against tuberculosis requires CD4+ T cells and CD8α+ lymphocytes DOI
Andrew Simonson, Joseph J. Zeppa, Allison N. Bucşan

et al.

The Journal of Experimental Medicine, Journal Year: 2025, Volume and Issue: 222(4)

Published: Jan. 17, 2025

Tuberculosis (TB) is a major health burden worldwide despite widespread intradermal (ID) BCG vaccination in newborns. We previously demonstrated that changing the route and dose from 5 × 105 CFUs ID to 107 i.v. resulted prevention of Mycobacterium tuberculosis (Mtb) infection TB disease highly susceptible nonhuman primates. Identifying immune mechanisms protection following will facilitate development more effective vaccines against TB. Here, we depleted lymphocyte subsets prior during Mtb challenge BCG-vaccinated macaques identify those necessary for protection. Depletion adaptive CD4 T cells, but not CD8αβ loss with increased burdens dissemination, indicating cells are critical BCG-mediated unconventional CD8α-expressing lymphocytes (NK innate CD4+CD8α+ double-positive cells) abrogated most BCG-immunized macaques, supporting further investigation into which these cell contribute after vaccination.

Language: Английский

Citations

2
Key advances in vaccine development for tuberculosis—success and challenges DOI Creative Commons
Rocky Lai,

Abiola F. Ogunsola,

Tasfia Rakib

et al.

npj Vaccines, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 13, 2023

Abstract Breakthrough findings in the clinical and preclinical development of tuberculosis (TB) vaccines have galvanized field suggest, for first time since bacille Calmette-Guérin (BCG), that a novel protective TB vaccine is on horizon. Here we highlight are pipeline review basis optimism both space. We describe immune signatures could act as immunological correlates protection (CoP) to facilitate comparison vaccines. Finally, discuss new animal models expected more faithfully model pathology complex responses observed human populations.

Language: Английский

Citations

31
Immune correlates of protection as a game changer in tuberculosis vaccine development DOI Creative Commons
Jing Wang, Xiao‐Yong Fan, Zhidong Hu

et al.

npj Vaccines, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 30, 2024

The absence of validated correlates protection (CoPs) hampers the rational design and clinical development new tuberculosis vaccines. In this review, we provide an overview potential CoPs in vaccine research. Major hindrances opportunities are then discussed. Based on recent progress, it is reasonable to anticipate that success ongoing efforts identify would be a game-changer development.

Language: Английский

Citations

11
Engineered Mycobacterium tuberculosis triple-kill-switch strain provides controlled tuberculosis infection in animal models DOI Creative Commons
Xin Wang,

Hongwei Su,

Joshua B. Wallach

et al.

Nature Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Human challenge experiments could accelerate tuberculosis vaccine development. This requires a safe Mycobacterium (Mtb) strain that can both replicate in the host and be reliably cleared. Here we genetically engineered Mtb strains encoding up to three kill switches: two mycobacteriophage lysin operons negatively regulated by tetracycline degron domain–NadE fusion, which induces ClpC1-dependent degradation of essential enzyme NadE, trimethoprim. The triple-kill-switch (TKS) showed similar growth kinetics antibiotic susceptibilities wild-type under permissive conditions but was rapidly killed vitro without trimethoprim doxycycline. It established infection mice receiving antibiotics cleared upon cessation treatment, no relapse observed infected severe combined immunodeficiency or Rag −/− mice. TKS had an escape mutation rate less than 10 −10 per genome generation. These findings suggest safe, effective candidate for human model.

Language: Английский

Citations

2
Humoral correlates of protection against Mycobacterium tuberculosis following intravenous Bacille Calmette-Guérin vaccination in rhesus macaques DOI Creative Commons
Edward B. Irvine, Patricia A. Darrah, Shu Wang

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(12), P. 111128 - 111128

Published: Oct. 15, 2024

Language: Английский

Citations

6
The frequency of CD38+ alveolar macrophages correlates with early control of M. tuberculosis in the murine lung DOI Creative Commons
Davide Pisu, Luana Johnston,

Joshua T. Mattila

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 2, 2024

Language: Английский

Citations

5
Function of hematopoiesis and bone marrow niche in inflammation and non-hematopoietic diseases DOI Creative Commons
Yuxiang Wang,

Zhao‐hua Deng,

Yuyan Li

et al.

Life Medicine, Journal Year: 2025, Volume and Issue: 4(3)

Published: March 26, 2025

Abstract Hematopoiesis and the behavior of hematopoietic stem progenitor cells (HSPCs) are regulated by bone marrow niche. Here, we introduce major niche cell types in their response to stress condition. We highlight adaptation inflammatory condition non-hematopoietic diseases, which not systematically summarized. These emerging data suggest targeting hematopoiesis may provide novel therapeutic target precisely control progression diseases.

Language: Английский

Citations

0
Antibiotic treatment modestly reduces protection against Mycobacterium tuberculosis reinfection in macaques DOI
Sharie Keanne C. Ganchua, Pauline Maiello, Michael C. Chao

et al.

Infection and Immunity, Journal Year: 2024, Volume and Issue: 92(4)

Published: March 22, 2024

ABSTRACT Concomitant immunity is generally defined as an ongoing infection providing protection against reinfection . Its role in prevention of tuberculosis (TB) caused by Mycobacterium (Mtb) supported epidemiological evidence humans well experimental mice and non-human primates (NHPs). Whether the presence live Mtb, rather than simply persistent antigen, necessary for concomitant TB still unclear. Here, we investigated whether Mtb plays a measurable control secondary infection. Using cynomolgus macaques, molecularly barcoded libraries, positron emission tomography-computed tomography (PET CT) imaging, flow cytometry, cytokine profiling, evaluated effect antibiotic treatment after primary on immunological response bacterial establishment, dissemination, burden post-secondary Our data provide that, this model, with antibiotics reduced inflammation lung but was not associated significant change or lymph nodes. Nonetheless, prior did result modest reduction reinfection: none seven antibiotic-treated animals demonstrated sterilizing reinfection, while four non-treated macaques were completely protected reinfection. These findings support that able to restrict establishment dissemination rechallenge compared naïve full extent non-antibiotic-treated macaques.

Language: Английский

Citations

3