Analysis of Cellular Phenotypes That Mediate Genetic Resistance to Tuberculosis Using a Radiation Bone Marrow Chimera Approach

Majorov, Konstantin; Eruslanov, Evgeny; Rubakova, Elvira I.; Kondratieva, Tatiana; Apt, Alexander S.

doi:10.1128/iai.73.9.6174-6178.2005

Cited by 10 publications

(5 citation statements)

References 28 publications

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“…The generation of bone marrow chimeras has been a useful tool to understand the cellular context of a genetic phenotype. Bone marrow chimeras have been used to identify the contribution of hematopoietic cells to a variety of preclinical disease models, including infectious diseases, transplantation, autoimmunity & asthma, and other tissue disorders [11][12][13][14][15][16][17][18][19]. At most institutions, irradiation is performed using a cesium 137 source, which has increasingly come under scrutiny as a potential domestic security risk owing to the possibility of their use in dirty bombs.…”

Section: Discussionmentioning

confidence: 99%

Generation of bone marrow chimeras using X-ray irradiation: comparison to cesium irradiation and use in immunotherapy

Eng

Orf

Perez

et al. 2020

JBM

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Bone marrow chimeras represent a key tool employed to understand biological contributions stemming from the hematopoietic versus the stromal compartment. In most institutions, cesium irradiators are used to lethally irradiate recipient animals prior to the injection of donor bone marrow. Cesium irradiators, however, have significant liabilities-including concerns around domestic security. Recently, X-ray irradiators have been implemented as a potential alternative to cesium sources. Only a small number of publications in the literature have attempted to compare these two modalities and, in most cases, the emphasis was on irradiation of human blood productions. We were able to find only a single study that directly compared X-ray and cesium technologies in the generation of murine bone marrow chimeras, a standard laboratory practice. This study focused on chimerism in the blood of recipient animals. In the present study, we begin by comparing cesium and X-ray based sources for irradiation, then transition to using X-ray-based systems for immunology models with an emphasis on immunotherapy of cancer in immunocompetent mouse models-specifically evaluating chimerism in the blood, spleen, and tumor microenvironment. While our data demonstrate that the two platforms are functionally comparable and suggest that X-ray based technology is a suitable alternative to cesium sources. We also highlight a difference in chimerism between the peripheral (blood, spleen) and tumor compartments that is observed using both technologies. While the overall degree of chimerism in the peripheral tissues is very high, the degree of chimerism in the tumor is cell type specific with T and NK cells showing lower chimerism than other cell types.

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Section: Discussionmentioning

confidence: 99%

Generation of bone marrow chimeras using X-ray irradiation: comparison to cesium irradiation and use in immunotherapy

Eng

Orf

Perez

et al. 2020

JBM

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“…1). Most susceptible mouse strains exhibit high PMN infiltration in the lungs once infected (83)(84)(85)(86), and inhibition of this infiltration improves survival (83). Mice that lack IFNγ exhibit high PMN infiltration as do mice lacking CD4 + T cells (70,78).…”

Section: Type II Interferon (Ifnγ)mentioning

confidence: 99%

Cytokines and Chemokines inMycobacterium tuberculosisInfection

Domingo-Gonzalez

Prince

Cooper

et al. 2017

Tuberculosis and the Tubercle Bacillus

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Chemokines and cytokines are critical for initiating and coordinating the organized and sequential recruitment and activation of cells into Mycobacterium tuberculosis-infected lungs. Correct mononuclear cellular recruitment and localization are essential to ensure control of bacterial growth without the development of diffuse and damaging granulocytic inflammation. An important block to our understanding of TB pathogenesis lies in dissecting the critical aspects of the cytokine/chemokine interplay in light of the conditional role these molecules play throughout infection and disease development. Much of the data highlighted in this review appears at first glance to be contradictory, but it is the balance between the cytokines and chemokines that is critical, and the "goldilocks" (not too much and not too little) phenomenon is paramount in any discussion of the role of these molecules in TB. Determination of how the key chemokines/cytokines and their receptors are balanced and how the loss of that balance can promote disease is vital to understanding TB pathogenesis and to identifying novel therapies for effective eradication of this disease.

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“…The capacity of the neutrophil‐dependent necrosis to really compromise immunity is further highlighted by the fact that the necrotic areas contain large numbers of non‐acid fast communities within biofilm‐like structures that are highly resistant to the effects of drugs . Lung PMN infiltrations are prominent in genetically susceptible strains of mice infected with Mtb , and the survival of Mtb‐infected, genetically susceptible DBA/2 mice is extended following depletion of PMNs using anti‐Ly6G, or neutralization of the PMN growth factor G‐CSF . Similar to DBA/2 mice, mouse strains that are genetically engineered to be immunodeficient also have prominent PMN‐associated pathology and can be rescued by PMN‐depletion.…”

Section: Neutrophil Recruitment and The Role In Pathologymentioning

confidence: 99%

The onset of adaptive immunity in the mouse model of tuberculosis and the factors that compromise its expression

Robinson

Orme

Cooper

2015

Immunological Reviews

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Mycobacterium tuberculosis (Mtb) has been evolving with its human host for over 50 000 years and is an exquisite manipulator of the human immune response. It induces both a strong inflammatory and a strong acquired immune response, and Mtb then actively regulates these responses to create an infectious lesion in the lung while maintaining a relatively ambulatory host. The CD4(+) T cell plays a critical yet contradictory role in this process by both controlling disseminated disease while promoting the development of the lesion in the lung that mediates transmission. In light of this manipulative relationship between Mtb and the human immune response, it is not surprising that our ability to vaccinate against tuberculosis (TB) has not been totally successful. To overcome the current impasse in vaccine development, we need to define the phenotype of CD4(+) T cells that mediate protection and to determine those bacterial and host factors that regulate the effective function of these cells. In this review, we describe the initiation and expression of T cells during TB as well as the fulminant inflammatory response that can compromise T-cell function and survival.

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Analysis of Cellular Phenotypes That Mediate Genetic Resistance to Tuberculosis Using a Radiation Bone Marrow Chimera Approach

Cited by 10 publications

References 28 publications

Generation of bone marrow chimeras using X-ray irradiation: comparison to cesium irradiation and use in immunotherapy

Generation of bone marrow chimeras using X-ray irradiation: comparison to cesium irradiation and use in immunotherapy

Cytokines and Chemokines inMycobacterium tuberculosisInfection

The onset of adaptive immunity in the mouse model of tuberculosis and the factors that compromise its expression

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