Animal Models of Mycobacteria Infection

Orme, Ian M.; Roberts, Alan D.

doi:10.1002/0471142735.im1905s30

Cited by 6 publications

(4 citation statements)

References 24 publications

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“…To understand the interplay between these two pathogens, we established an in vivo model of coinfection wherein BALB/c mice were aerosolized with Mtb at ~ 200 Colony‐Forming Unit (CFU). This lead to granuloma formation in 4 weeks, marking the onset of active tuberculosis [9,23], followed by intravenous infection of C . albicans, leading to systemic candidiasis [22].…”

Section: Resultsmentioning

confidence: 99%

Pre‐existing mycobacterial infection modulates Candida albicans‐driven pyroptosis

et al. 2021

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Active tuberculosis patients are at high risk of coinfection with opportunistic fungal pathogen Candida albicans. However, the molecular mechanisms that orchestrate pathogenesis of Mycobacterium tuberculosis (Mtb)‐C. albicans coinfection remain elusive. In the current study, we utilize a mouse model to demonstrate that Mtb promotes a macrophage environment that is conducive for C. albicans survival. Mtb‐dependent protein kinase Cζ‐WNT signalling axis induces expression of an E3 ubiquitin ligase, constitutive photomorphogenesis protein 1 (COP1). A secondary infection of C. albicans in such Mtb‐infected macrophages causes COP1 to mediate the proteasomal degradation of interferon regulatory factor 9 (IRF9), a cardinal factor that we identified to arbitrate an inflammatory programmed cell death, pyroptosis. In vivo experiments mimicking a pre‐existing Mtb infection demonstrate that inhibition of pyroptosis in mice results in increased C. albicans burden and aberrant lung tissue architecture, leading to increased host mortality. Together, our study reveals the crucial role of pyroptosis regulation for manifesting a successful C. albicans–Mtb coinfection.

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Section: Resultsmentioning

confidence: 99%

Pre‐existing mycobacterial infection modulates Candida albicans‐driven pyroptosis

et al. 2021

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“…Three weeks after second dose of immunization, low dose of H37Rv aerosol infection was given to two groups of all the immunized and age matched control animals. Mice were exposed to the aerosol generated by Glass-Col inhalation exposure system to establish 200–400 bacilli of H37Rv per mouse [35].…”

Section: Methodsmentioning

confidence: 99%

Aerosol immunization by alginate coated mycobacterium (BCG/MIP) particles provide enhanced immune response and protective efficacy than aerosol of plain mycobacterium against M.tb. H37Rv infection in mice

et al. 2019

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Background With the aim of preparing a more effective, safe and economical vaccine for tuberculosis, inhalable live mycobacterium formulations were evaluated. Methods Alginate particles in the size range of 2–4 μm were prepared by encapsulating live Bacille Calmette–Guérin (BCG) and “ Mycobacterium indicus pranii” (MIP). These particles were characterized for their size, stability and release profile. Mice were immunized with liquid aerosol or dry powder aerosol (DPA) alginate encapsulated mycobacterium particles and their in-vitro recall response and infection with mycobacterium H37Rv were investigated. Results It was found that the DPA of alginate encapsulated mycobacterium particles invoked superior immune response and provided higher protection in mice than the liquid aerosol. The BCG encapsulated in alginate particles (BEAP) and MIP encapsulated in alginate particles (MEAP) were engulfed by bone marrow dendritic cells (BMDCs) and co-localized with lysosome. The MEAP/BEAP activated BMDCs exhibited higher chemotaxis movement and had enhanced ability of antigen presentation to T cells. The in-vitro recall response of BEAP/MEAP immunized mice when compared in terms of proliferation index and Interferon gamma (IFN-gamma) released by splenocytes and mediastinal lymph node cells was found to be higher than mice immunized by liquid aerosol of BCG/MIP. Finally, different groups of immunized mice were infected with M. tb H37Rv and after 16 weeks the Colony forming units (CFUs) in lung and spleen estimated. The bacilli burden in the BEAP/MEAP immunized mice was significantly less than the respective liquid aerosol immunized mice and the histopathology of BEAP/MEAP immunized mice lungs showed very little damage. Conclusions These inhale-able vaccines formulation of alginate coated live mycobacterium are more immunogenic as compared to the aerosol of bacilli and they provide better protection in mice when infected with H37Rv. Electronic supplementary material The online version of this article (10.1186/s12879-019-4157-2) contains supplementary material, which is available to authorized users.

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“…Mice were infected with M. avium 25291 (ATTC) at a dose of 1 × 10 6 cfu by lateral tail vein injection. The level of bacteria in specific organs was determined by homogenizing the organs and plating on agar and counting colonies . Some infected WT mice were treated with aminoguanidine hemisulfate (Sigma‐Aldrich) at 2.5 g/100 mL in the drinking water for defined periods of time; control mice received water without drug.…”

Section: Methodsmentioning

confidence: 99%

Nitric oxide inhibits the accumulation of CD4⁺CD44^hiTbet⁺CD69^loT cells in mycobacterial infection

et al. 2012

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Summary Animals lacking the inducible nitric oxide synthase gene (nos2−/−) are less susceptible to M. avium strain 25291 and lack nitric oxide-mediated immunomodulation of CD4+ T cells. Here we show that the absence of nos2 results in increased accumulation of neutrophils and both CD4+ and CD8+ T cells within the M. avium-containing granuloma. Examination of the T-cell phenotype in M. avium-infected mice demonstrated that CD4+CD44hi effector T cells expressing the Th1 transcriptional regulator T-bet (T-bet+) were specifically reduced by the presence of nitric oxide. Importantly, the T-bet+ effector population could be separated into CD69hi and CD69lo populations, with the CD69lo population only able to accumulate during chronic infection within infected nos2−/− mice. Transcriptomic comparison between CD4+CD44hiCD69hi and CD4+CD44hiCD69lo populations revealed that CD4+CD44hiCD69lo cells had higher expression of the integrin itgb1/itga4 (VLA-4, CD49d/CD29). Inhibition of Nos2 activity allowed increased accumulation of the CD4+CD44hiT-bet+CD69lo population in WT mice as well as increased expression of VLA-4. These data support the hypothesis that effector T cells in mycobacterial granulomata are not a uniform effector population but exist in distinct subsets with differential susceptibility to the regulatory effects of nitric oxide.

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Animal Models of Mycobacteria Infection

Cited by 6 publications

References 24 publications

Pre‐existing mycobacterial infection modulates Candida albicans‐driven pyroptosis

Pre‐existing mycobacterial infection modulates Candida albicans‐driven pyroptosis

Aerosol immunization by alginate coated mycobacterium (BCG/MIP) particles provide enhanced immune response and protective efficacy than aerosol of plain mycobacterium against M.tb. H37Rv infection in mice

Nitric oxide inhibits the accumulation of CD4⁺CD44^hiTbet⁺CD69^loT cells in mycobacterial infection

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Animal Models of Mycobacteria Infection

Cited by 6 publications

References 24 publications

Pre‐existing mycobacterial infection modulates Candida albicans‐driven pyroptosis

Pre‐existing mycobacterial infection modulates Candida albicans‐driven pyroptosis

Aerosol immunization by alginate coated mycobacterium (BCG/MIP) particles provide enhanced immune response and protective efficacy than aerosol of plain mycobacterium against M.tb. H37Rv infection in mice

Nitric oxide inhibits the accumulation of CD4+CD44hiTbet+CD69loT cells in mycobacterial infection

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Nitric oxide inhibits the accumulation of CD4⁺CD44^hiTbet⁺CD69^loT cells in mycobacterial infection