Relative Levels of M-CSF and GM-CSF Influence the Specific Generation of Macrophage Populations during Infection with Mycobacterium tuberculosis

ABSTRACT Mycobacterium bovis bacillus Calmette-Guérin (BCG) currently remains the only licensed vaccine for the prevention of tuberculosis. In this study, we used a newly described flow cytometric technique to monitor changes in cell populations accumulating in the lungs and lymph nodes of naïve and vaccinated guinea pigs challenged by low-dose aerosol infection with virulent Mycobacterium tuberculosis. As anticipated, vaccinated guinea pigs controlled the growth of the challenge infection more efficiently than controls did. This early phase of bacterial control in immune animals was associated with increased accumulation of CD4 and CD8 T cells, including cells expressing the activation marker CD45, as well as macrophages expressing class II major histocompatibility complex molecules. As the infection continued, the numbers of T cells in the lungs of vaccinated animals waned, whereas the numbers of these cells expressing CD45 increased. Whereas BCG vaccination reduced the influx of heterophils (neutrophils) into the lungs, an early B-cell influx was observed in these vaccinated animals. Overall, vaccine protection was associated with reduced pathology and lung damage in the vaccinated animals. These data provide the first direct evidence that BCG vaccination accelerates the influx of protective T-cell and macrophage populations into the infected lungs, diminishes the accumulation of nonprotective cell populations, and reduces the severity of lung pathology.

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Heterogeneous GM-CSF signaling in macrophages is associated with control of Mycobacterium tuberculosis

Nature Communications ◽

10.1038/s41467-019-10065-8 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 9

Author(s):

Bryan D. Bryson ◽

Tracy R. Rosebrock ◽

Fikadu G. Tafesse ◽

Christopher Y. Itoh ◽

Armel Nibasumba ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Gm Csf

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The Glycan-Rich Outer Layer of the Cell Wall of Mycobacterium tuberculosis Acts as an Antiphagocytic Capsule Limiting the Association of the Bacterium with Macrophages

Infection and Immunity ◽

10.1128/iai.72.10.5676-5686.2004 ◽

2004 ◽

Vol 72 (10) ◽

pp. 5676-5686 ◽

Cited By ~ 86

Author(s):

Richard W. Stokes ◽

Raymond Norris-Jones ◽

Donald E. Brooks ◽

Terry J. Beveridge ◽

Dan Doxsee ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Surface Hydrophobicity ◽

Host Cells ◽

Microbial Pathogens ◽

Mammalian Host ◽

Human Macrophage ◽

Bacterial Surface ◽

Important Virulence Factor ◽

Complement Receptor 3 ◽

Macrophage Populations

ABSTRACT Mycobacterium tuberculosis, the causative agent of tuberculosis, is a facultative intracellular pathogen that infects macrophages and other host cells. We show that sonication of M. tuberculosis results in the removal of material from the surface capsule-like layer of the bacteria, resulting in an enhanced propensity of the bacteria to bind to macrophages. This effect is observed with disparate murine and human macrophage populations though, interestingly, not with freshly explanted alveolar macrophages. Enhanced binding to macrophages following sonication is significantly greater within members of the M. tuberculosis family (pathogens) than within the Mycobacterium avium complex (opportunistic pathogens) or for Mycobacterium smegmatis (saprophyte). Sonication does not affect the viability or the surface hydrophobicity of M. tuberculosis but does result in changes in surface charge and in the binding of mannose-specific lectins to the bacterial surface. The increased binding of sonicated M. tuberculosis was not mediated through complement receptor 3. These results provide evidence that the surface capsule on members of the M. tuberculosis family may be an important virulence factor involved in the survival of M. tuberculosis in the mammalian host. They also question the view that M. tuberculosis is readily ingested by any macrophage it encounters and support the contention that M. tuberculosis, like many other microbial pathogens, has an antiphagocytic capsule that limits and controls the interaction of the bacterium with macrophages.

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Modulation of pulmonary DC function by vaccine-encoded GM-CSF enhances protective immunity against Mycobacterium tuberculosis infection

European Journal of Immunology ◽

10.1002/eji.200939665 ◽

2009 ◽

Vol 40 (1) ◽

pp. 153-161 ◽

Cited By ~ 34

Author(s):

Jonathan K. Nambiar ◽

Anthony A. Ryan ◽

Carlyn U. Kong ◽

Warwick J. Britton ◽

James A. Triccas

Keyword(s):

Mycobacterium Tuberculosis ◽

Protective Immunity ◽

Tuberculosis Infection ◽

Mycobacterium Tuberculosis Infection ◽

Gm Csf ◽

Dc Function

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iNKT Cell Production of GM-CSF Controls Mycobacterium tuberculosis

PLoS Pathogens ◽

10.1371/journal.ppat.1003805 ◽

2014 ◽

Vol 10 (1) ◽

pp. e1003805 ◽

Cited By ~ 68

Author(s):

Alissa C. Rothchild ◽

Pushpa Jayaraman ◽

Cláudio Nunes-Alves ◽

Samuel M. Behar

Keyword(s):

Mycobacterium Tuberculosis ◽

Inkt Cell ◽

Cell Production ◽

Gm Csf

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Comparative Analysis of Cytokine mRNA Expressions in Human Tissues with Mycobacterium tuberculosis Infection

10.20944/preprints202105.0347.v1 ◽

2021 ◽

Author(s):

Sung-Bae Park ◽

Heechul Park ◽

Yoon-Sung Choi ◽

Ji Young Park ◽

Dongsup Lee ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Mrna Expression ◽

The Body ◽

Molecular Diagnostic ◽

Human Tissues ◽

Immune Markers ◽

Cytokine Mrna ◽

Expression Levels ◽

Gm Csf ◽

Mrna Expression Levels

In the present study, we aimed to investigate whether an automated molecular diagnostic method based on PCR-reverse blot hybridization assay can discriminate between human Mycobacterium tuberculosis (MTB)-positive and -negative FFPE tissues and to compare the relative mRNA expression levels of various host immune markers between MTB-infected and uninfected human tissues using quantitative reverse transcription (qRT) PCR. A total of 52 human FFPE tissue samples from various regions of the body, including the lungs, lymph nodes, tendons, colon, and appendix, were collected and used for the molecular identification of Mycobacterium species and analysis of cytokine mRNA expression. As a result, IFN-γ, TNF-α, IP-10, CXCL9, CXCL11, and GM-CSF mRNA expression levels in MTB-infected tissues were significantly higher than those in uninfected samples. Additionally, the differences in the mRNA expression levels of IFN-γ, CXCL9, and GM-CSF between MTB-infected and uninfected tissues were statistically significant were statistically significant (p < 0.05). Correlation curve analysis indicated that the mRNA expression of IFN-γ was inversely proportional to that of IP-10 and that the mRNA expression levels of IFN-γ, TNF-α, CXCL9, CXCL11, GM-CSF, and TNFR were proportional and well-correlated. Furthermore, to establish marker profiles for detecting MTB infection, the statistically significant expression levels of three markers were combined. We confirmed that the combined profile of IFN-γ, CXCL9, and GM-CSF expression levels was statistically significant (P < 0.001). Although the mRNA expression patterns of host immune markers may vary according to MTB infection status, these patterns may be highly correlated and can be simultaneously used as an additional indicator for diagnosing TB.

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Transcriptional regulation of voltage-gated sodium channels contributes to GM-CSF induced pain

10.1101/386698 ◽

2018 ◽

Author(s):

Fan Zhang ◽

Yiying Wang ◽

Dandan Zhang ◽

Xizhenzi Fan ◽

Hao Han ◽

...

Keyword(s):

Cancer Pain ◽

Thermal Hyperalgesia ◽

Bone Cancer ◽

Bone Cancer Pain ◽

Drg Neurons ◽

Voltage Gated ◽

Gm Csf ◽

Damage Sensing ◽

Voltage Gated Sodium Channels ◽

Macrophage Populations

AbstractGranolocyte-macrophage colony stimulating factor (GM-CSF) induces production of granulocyte and macrophage populations from the hematopoietic progenitor cells; it is one of the most common growth factors in the blood. GM-CSF is also involved in bone cancer pain development by regulating tumor-nerve interactions, remodeling of peripheral nerves and sensitization of damage-sensing (nociceptive) nerves. However, the precise mechanism for GM-CSF-dependent pain is unclear. In this study, we found that GM-CSF is highly expressed in human malignant osteosarcoma. Rats implanted with bone cancer cells develop mechanical and thermal hyperalgesia but antagonizing GM-CSF in these animals significantly reduced such hypersensitivity. Nociceptor-specific voltage gated Na+channels Nav1.7, Nav1.8 and Nav1.9 were found to be selectively up-regulated in rat DRG neurons treated with GM-CSF, which resulted in enhanced excitability. GM-CSF activated the Jak2 and Stat3 signaling pathway which promoted the transcription of Nav1.7-1.9 in DRG neurons. Accordingly targeted knocking down either Nav1.7-1.9 or Jak2/Stat3 in DRG neurons alleviated the hyperalgesia in rats. Our findings describe a new bone cancer pain mechanism and provide a new insight into the physiological and pathological functions of GM-CSF.

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