The Global Success of Mycobacterium tuberculosis Modern Beijing Family Is Driven by a Few Recently Emerged Strains

Zhu, Chendi; Yang, Tingting; Yin, Jinfeng; Jiang, Hui; Takiff, Howard; Gao, Qian; Liu, Qingyun; Li, Weimin

doi:10.1128/spectrum.03339-22

Cited by 7 publications

(11 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The tremendous success of Mtb as a pathogen can be explained by its co-evolution with that of the host. Strains from the Beijing family are among the most successful, as demonstrated by their global distribution and the recurrent outbreaks they cause ( 52 ). This success is partially due to their exquisite ability to manipulate the host’s immune system.…”

Section: Discussionmentioning

confidence: 99%

Dual neutrophil subsets exacerbate or suppress inflammation in tuberculosis via IL-1β or PD-L1

Doz-Deblauwe,

Bounab,

Carreras

et al. 2024

Life Sci. Alliance

View full text Add to dashboard Cite

Neutrophils can be beneficial or deleterious during tuberculosis (TB). Based on the expression of MHC-II and programmed death ligand 1 (PD-L1), we distinguished two functionally and transcriptionally distinct neutrophil subsets in the lungs of mice infected with mycobacteria. Inflammatory [MHC-II−, PD-L1lo] neutrophils produced inflammasome-dependent IL-1β in the lungs in response to virulent mycobacteria and “accelerated” deleterious inflammation, which was highly exacerbated in IFN-γR−/−mice. Regulatory [MHC-II+, PD-L1hi] neutrophils “brake” inflammation by suppressing T-cell proliferation and IFN-γ production. Such beneficial regulation, which depends on PD-L1, is controlled by IFN-γR signaling in neutrophils. The hypervirulent HN878 strain from the Beijing genotype curbed PD-L1 expression by regulatory neutrophils, abolishing the braking function and driving deleterious hyperinflammation in the lungs. These findings add a layer of complexity to the roles played by neutrophils in TB and may explain the reactivation of this disease observed in cancer patients treated with anti-PD-L1.

show abstract

Section: Discussionmentioning

confidence: 99%

Dual neutrophil subsets exacerbate or suppress inflammation in tuberculosis via IL-1β or PD-L1

Doz-Deblauwe,

Bounab,

Carreras

et al. 2024

Life Sci. Alliance

View full text Add to dashboard Cite

show abstract

“…The tremendous success of Mtb as a pathogen can be explained by its co-evolution with that of the host. Strains from the Beijing family are among the most successful, as demonstrated by their global distribution and the recurrent outbreaks they cause ( 53 ). This success is partially due to their exquisite ability to manipulate the host’s immune system.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil subsets play dual roles in tuberculosis by producing inflammasome dependent-IL-1β or suppressing T-cells via PD-L1

Doz-Deblauwe,

Bounab,

Carreras

et al. 2023

Preprint

View full text Add to dashboard Cite

Neutrophils can be beneficial or deleterious during tuberculosis (TB). Based on the expression of MHC-II and programmed death ligand 1 (PD-L1), we distinguished two functionally and transcriptionally distinct neutrophil subsets in the lungs of mice infected with mycobacteria. Inflammatory [MHC-II-, PD-L1lo] neutrophils produced inflammasome-dependent IL-1β in the lungs in response to virulent mycobacteria and “accelerated” deleterious inflammation, which was highly exacerbated in IFN-γR-/-mice. Regulatory [MHC-II+, PD-L1hi] neutrophils “brake” inflammation by suppressing T-cell proliferation and IFN-γ production. Such beneficial regulation, which depends on PD-L1, is controlled by IFN-γR signaling in neutrophils. The hypervirulent HN878 strain from the Beijing genotype curbed PD-L1 expression by regulatory neutrophils, abolishing the braking function and driving deleterious hyper-inflammation in the lungs. These findings add a layer of complexity to the roles played by neutrophils in TB and may explain the reactivation of this disease observed in cancer patients treated with anti-PD-L1.One Sentence SummaryRegulatory and inflammatory neutrophil subsets play inverse roles in tuberculosis.

show abstract

“…It is well known that, even after becoming infected with M. tuberculosis , the natural immunity generated is not protective, although natural infection occurs via aerosol [ 44 ]. However, CDC WT was chosen as the backbone for this vaccine due to its immunogenic nature, despite being from a marginal lineage as compared to the epidemic-associated, BCG-resistant Bejing strains of M. tuberculosis [ 45 , 46 ]. M. tuberculosis CDC1551 has been shown to cause increased seroconversion without increased disease compared to other clinical isolates and, through a potent and early stimulation of Th1 responses in hosts, is thought to limit its own infection and have longer survival times despite having similar bacterial burdens to other strains [ 27 , 28 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…From these studies, we chose mosR as a deletion candidate, as it was the most highly upregulated gene in murine lungs at multiple timepoints (28,45, and 60 days post-infection) when compared to M. tuberculosis in culture; upon further study, it was revealed to be an operon controlling gene involved in late-stage mycobacterial survival [17,19]. The single deletion of mosR in the H37Rv backbone was shown to be highly attenuated via the aerosol route and the single deletion in the CDC1551 backbone was shown to be a safe and effective vaccine in a previous study [19,20].…”

Section: Introductionmentioning

confidence: 99%

The Immunogenicity and Safety of Mycobacterium tuberculosis-mosR-Based Double Deletion Strain in Mice

Hildebrand,

Hansen,

Kingstad-Bakke

et al. 2023

Microorganisms

View full text Add to dashboard Cite

Mycobacterium tuberculosis (M. tuberculosis) remains a significant global health threat, accounting for ~1.7 million deaths annually. The efficacy of the current vaccine, M. bovis BCG, ranges from 0 to 80% in children and does not prevent adulthood tuberculosis. We explored the immune profile and safety of a live-attenuated M. tuberculosis construct with double deletions of the mosR and echA7 genes, where previously, single mutations were protective against an M. tuberculosis aerosol challenge. Over 32 weeks post-vaccination (WPV), immunized mice with M. tuberculosisΔmosRΔechA7 (double mutant) were sacrificed to evaluate the vaccine persistence, histopathology, and immune responses. Interestingly, despite similar tissue colonization between the vaccine double mutant and wild-type M. tuberculosis, the vaccine construct showed a greater reaction to the ESAT-6, TB.10, and Ag85B antigens with peptide stimulation. Additionally, there was a greater number of antigen-specific CD4 T cells in the vaccine group, accompanied by significant polyfunctional T-cell responses not observed in the other groups. Histologically, mild but widely distributed inflammatory responses were recorded in the livers and lungs of the immunized animals at early timepoints, which turned into organized inflammatory foci via 32WPV, a pathology not observed in BCG-immunized mice. A lower double-mutant dose resulted in significantly less tissue colonization and less tissue inflammation. Overall, the double-mutant vaccine elicited robust immune responses dominated by antigen-specific CD4 T cells, but also triggered tissue damage and vaccine persistence. The findings highlight key features associated with the immunogenicity and safety of the examined vaccine construct that can benefit the future evaluation of other live vaccines.

show abstract

The Global Success of Mycobacterium tuberculosis Modern Beijing Family Is Driven by a Few Recently Emerged Strains

Abstract: The recent population dynamics of the global tuberculosis epidemic are heavily shaped by Mycobacterium tuberculosis complex (MTBC) strains with enhanced transmissibility. The infamous Beijing family strain stands out because it has rapidly spread throughout the world.

Cited by 7 publications

References 58 publications

Dual neutrophil subsets exacerbate or suppress inflammation in tuberculosis via IL-1β or PD-L1

Dual neutrophil subsets exacerbate or suppress inflammation in tuberculosis via IL-1β or PD-L1

Neutrophil subsets play dual roles in tuberculosis by producing inflammasome dependent-IL-1β or suppressing T-cells via PD-L1

The Immunogenicity and Safety of Mycobacterium tuberculosis-mosR-Based Double Deletion Strain in Mice

Contact Info

Product

Resources

About