Iron limitation in M. tuberculosis has broad impact on central carbon metabolism DOI Creative Commons
Monique E. Theriault, Davide Pisu, Kaley M. Wilburn

et al.

Communications Biology, Journal Year: 2022, Volume and Issue: 5(1)

Published: July 9, 2022

Abstract Mycobacterium tuberculosis ( Mtb ), the cause of human pulmonary disease (TB), contributes to approximately 1.5 million deaths every year. Prior work has established that lipids are actively catabolized by in vivo and fulfill major roles physiology pathogenesis. We conducted a high-throughput screen identify inhibitors survival its host macrophage. One hit compounds identified this screen, sAEL057, demonstrates highest activity on growth conditions where cholesterol was primary carbon source. Transcriptional functional data indicate sAEL057 limits ’s access iron acting as an chelator. Furthermore, pharmacological genetic inhibition acquisition results dysregulation catabolism, revealing previously unappreciated linkage between these pathways. Characterization sAEL057’s mode action argues metabolic regulation reveals vulnerabilities those pathways impact central metabolism.

Language: Английский

Single-cell profiling identifies ACE + granuloma macrophages as a nonpermissive niche for intracellular bacteria during persistent Salmonella infection DOI Creative Commons
Trung H. M. Pham, Yuan Xue, Susan Brewer

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(1)

Published: Jan. 6, 2023

Macrophages mediate key antimicrobial responses against intracellular bacterial pathogens, such as Salmonella enterica . Yet, they can also act a permissive niche for these pathogens to persist in infected tissues within granulomas, which are immunological structures composed of macrophages and other immune cells. We apply single-cell transcriptomics investigate macrophage functional diversity during persistent S. serovar Typhimurium ( S Tm) infection mice. identify determinants heterogeneity spleens describe populations distinct phenotypes, programming, spatial localization. Using an Tm mutant with impaired ability polarize we find that angiotensin-converting enzyme (ACE) defines granuloma population is nonpermissive bacteria, their abundance anticorrelates tissue burden. Disruption pathogen control by neutralizing TNF linked preferential depletion ACE + tissues. Thus, have limited capacity serve cellular bacteria establish infection.

Language: Английский

Citations

17
Pathological roles of macrophages in Leishmania infections DOI Creative Commons
Yasuyuki Goto, Haruka Mizobuchi

Parasitology International, Journal Year: 2023, Volume and Issue: 94, P. 102738 - 102738

Published: Feb. 3, 2023

Macrophages are the major host cells for Leishmania parasites, and determine fate of infection by either limiting or allowing growth resulting in development control leishmaniasis, respectively. They also play important roles causing pathological outcomes during infection. The pathophysiology is complex include a wide variety molecular cellular responses including enhancement inflammatory releasing cytokines, damages to surrounding reactive oxygen species, disordered phagocytosis other cells. It note that disease severity leishmaniasis sometimes does not correlate with parasite burdens, indicating macrophages necessarily linked their parasite-killing activities often defined M1/M2 status. Here, we review focus on mechanisms development.

Language: Английский

Citations

17
CD4+ T cells re-wire granuloma cellularity and regulatory networks to promote immunomodulation following Mtb reinfection DOI Creative Commons
Joshua D. Bromley, Sharie Keanne C. Ganchua, Sarah K. Nyquist

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(10), P. 2380 - 2398.e6

Published: Aug. 29, 2024

Language: Английский

Citations

8
No smoke without fire: the impact of cigarette smoking on the immune control of tuberculosis DOI Creative Commons
Diana H. Quan,

Alexander J. Kwong,

Philip M. Hansbro

et al.

European Respiratory Review, Journal Year: 2022, Volume and Issue: 31(164), P. 210252 - 210252

Published: June 7, 2022

Cigarette smoke (CS) exposure is a key risk factor for both active and latent tuberculosis (TB). It associated with delayed diagnosis, more severe disease progression, unfavourable treatment outcomes relapse after treatment. Critically, CS common in heavily populated areas high burden of TB, such as China, India the Russian Federation. therefore prudent to evaluate interventions TB while taking into account immunological impacts exposure. This review mechanistic examination how impairs innate barrier defences, well alveolar macrophage, neutrophil, dendritic cell T-cell functions, context infection disease.

Language: Английский

Citations

24
Iron limitation in M. tuberculosis has broad impact on central carbon metabolism DOI Creative Commons
Monique E. Theriault, Davide Pisu, Kaley M. Wilburn

et al.

Communications Biology, Journal Year: 2022, Volume and Issue: 5(1)

Published: July 9, 2022

Abstract Mycobacterium tuberculosis ( Mtb ), the cause of human pulmonary disease (TB), contributes to approximately 1.5 million deaths every year. Prior work has established that lipids are actively catabolized by in vivo and fulfill major roles physiology pathogenesis. We conducted a high-throughput screen identify inhibitors survival its host macrophage. One hit compounds identified this screen, sAEL057, demonstrates highest activity on growth conditions where cholesterol was primary carbon source. Transcriptional functional data indicate sAEL057 limits ’s access iron acting as an chelator. Furthermore, pharmacological genetic inhibition acquisition results dysregulation catabolism, revealing previously unappreciated linkage between these pathways. Characterization sAEL057’s mode action argues metabolic regulation reveals vulnerabilities those pathways impact central metabolism.

Language: Английский

Citations

24