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Gr1(int)CD11b+ myeloid-derived suppressor cells in Mycobacterium tuberculosis infection.

Obregón-Henao A, Henao-Tamayo M, Orme IM, Ordway DJ - PLoS ONE (2013)

Bottom Line: Both populations of Gr1(+)CD11b(+) cells expressed high levels of arginase-1, and IL-17, additional markers of myeloid derived suppressor cells.Our results showed that both Gr1(hi) and Gr1(int) cells were able to induce activation and proliferation of CD4+ T cells.However this response was reduced as the ratio of CD4(+) T to Gr1(+) cells increased.

View Article: PubMed Central - PubMed

Affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.

ABSTRACT

Background: Tuberculosis is one of the world's leading killers, stealing 1.4 million lives and causing 8.7 million new and relapsed infections in 2011. The only vaccine against tuberculosis is BCG which demonstrates variable efficacy in adults worldwide. Human infection with Mycobacterium tuberculosis results in the influx of inflammatory cells to the lung in an attempt to wall off bacilli by forming a granuloma. Gr1(int)CD11b(+) cells are called myeloid-derived suppressor cells (MDSC) and play a major role in regulation of inflammation in many pathological conditions. Although MDSC have been described primarily in cancer their function in tuberculosis remains unknown. During M. tuberculosis infection it is crucial to understand the function of cells involved in the regulation of inflammation during granuloma formation. Understanding their relative impact on the bacilli and other cellular phenotypes is necessary for future vaccine and drug design.

Methodology/principal findings: We compared the bacterial burden, lung pathology and Gr1(int)CD11b(+) myeloid-derived suppressor cell immune responses in M. tuberculosis infected NOS2-/-, RAG-/-, C3HeB/FeJ and C57/BL6 mice. Gr-1(+) cells could be found on the edges of necrotic lung lesions in NOS2-/-, RAG-/-, and C3HeB/FeJ, but were absent in wild-type mice. Both populations of Gr1(+)CD11b(+) cells expressed high levels of arginase-1, and IL-17, additional markers of myeloid derived suppressor cells. We then sorted the Gr1(hi) and Gr1(int) populations from M. tuberculosis infected NOS-/- mice and placed the sorted both Gr1(int) populations at different ratios with naïve or M. tuberculosis infected splenocytes and evaluated their ability to induce activation and proliferation of CD4+T cells. Our results showed that both Gr1(hi) and Gr1(int) cells were able to induce activation and proliferation of CD4+ T cells. However this response was reduced as the ratio of CD4(+) T to Gr1(+) cells increased. Our results illustrate a yet unrecognized interplay between Gr1(+) cells and CD4(+) T cells in tuberculosis.

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Related in: MedlinePlus

Gr1int and Gr1hi cells sorted from M. tuberculosis infected NOS-/- mice expressed arginase I and IL-17.Specific populations of Gr1int or Gr1hi cells were sorted from infected NOS-/- mice in an attempt to further characterize Gr1int and Gr1hi cell function during tuberculosis using flow cytometry. Panel A, demonstrates pre-sorted Gr1+CD11b+ cells which were then further characterized. Gr1hi and Gr1int sorted cells (B, C) both demonstrated high expression of arginase I and IL-17. Panel D shows the isotype controls for arginase-1 and IL-17A.
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pone-0080669-g006: Gr1int and Gr1hi cells sorted from M. tuberculosis infected NOS-/- mice expressed arginase I and IL-17.Specific populations of Gr1int or Gr1hi cells were sorted from infected NOS-/- mice in an attempt to further characterize Gr1int and Gr1hi cell function during tuberculosis using flow cytometry. Panel A, demonstrates pre-sorted Gr1+CD11b+ cells which were then further characterized. Gr1hi and Gr1int sorted cells (B, C) both demonstrated high expression of arginase I and IL-17. Panel D shows the isotype controls for arginase-1 and IL-17A.

Mentions: In an attempt to further characterize Gr1int and Gr1hi cell function during tuberculosis infection we conducted cell sorting of Gr1int and Gr1hi cells from naïve and infected NOS-/- mice. Figure 6 A, demonstrates pre-sorted Gr1+CD11b+ cells which were then further characterized. Gr1hi and Gr1int sorted cells (Figure 6 B, C) both demonstrated high expression of arginase-1 and IL-17.


Gr1(int)CD11b+ myeloid-derived suppressor cells in Mycobacterium tuberculosis infection.

Obregón-Henao A, Henao-Tamayo M, Orme IM, Ordway DJ - PLoS ONE (2013)

Gr1int and Gr1hi cells sorted from M. tuberculosis infected NOS-/- mice expressed arginase I and IL-17.Specific populations of Gr1int or Gr1hi cells were sorted from infected NOS-/- mice in an attempt to further characterize Gr1int and Gr1hi cell function during tuberculosis using flow cytometry. Panel A, demonstrates pre-sorted Gr1+CD11b+ cells which were then further characterized. Gr1hi and Gr1int sorted cells (B, C) both demonstrated high expression of arginase I and IL-17. Panel D shows the isotype controls for arginase-1 and IL-17A.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815237&req=5

pone-0080669-g006: Gr1int and Gr1hi cells sorted from M. tuberculosis infected NOS-/- mice expressed arginase I and IL-17.Specific populations of Gr1int or Gr1hi cells were sorted from infected NOS-/- mice in an attempt to further characterize Gr1int and Gr1hi cell function during tuberculosis using flow cytometry. Panel A, demonstrates pre-sorted Gr1+CD11b+ cells which were then further characterized. Gr1hi and Gr1int sorted cells (B, C) both demonstrated high expression of arginase I and IL-17. Panel D shows the isotype controls for arginase-1 and IL-17A.
Mentions: In an attempt to further characterize Gr1int and Gr1hi cell function during tuberculosis infection we conducted cell sorting of Gr1int and Gr1hi cells from naïve and infected NOS-/- mice. Figure 6 A, demonstrates pre-sorted Gr1+CD11b+ cells which were then further characterized. Gr1hi and Gr1int sorted cells (Figure 6 B, C) both demonstrated high expression of arginase-1 and IL-17.

Bottom Line: Both populations of Gr1(+)CD11b(+) cells expressed high levels of arginase-1, and IL-17, additional markers of myeloid derived suppressor cells.Our results showed that both Gr1(hi) and Gr1(int) cells were able to induce activation and proliferation of CD4+ T cells.However this response was reduced as the ratio of CD4(+) T to Gr1(+) cells increased.

View Article: PubMed Central - PubMed

Affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.

ABSTRACT

Background: Tuberculosis is one of the world's leading killers, stealing 1.4 million lives and causing 8.7 million new and relapsed infections in 2011. The only vaccine against tuberculosis is BCG which demonstrates variable efficacy in adults worldwide. Human infection with Mycobacterium tuberculosis results in the influx of inflammatory cells to the lung in an attempt to wall off bacilli by forming a granuloma. Gr1(int)CD11b(+) cells are called myeloid-derived suppressor cells (MDSC) and play a major role in regulation of inflammation in many pathological conditions. Although MDSC have been described primarily in cancer their function in tuberculosis remains unknown. During M. tuberculosis infection it is crucial to understand the function of cells involved in the regulation of inflammation during granuloma formation. Understanding their relative impact on the bacilli and other cellular phenotypes is necessary for future vaccine and drug design.

Methodology/principal findings: We compared the bacterial burden, lung pathology and Gr1(int)CD11b(+) myeloid-derived suppressor cell immune responses in M. tuberculosis infected NOS2-/-, RAG-/-, C3HeB/FeJ and C57/BL6 mice. Gr-1(+) cells could be found on the edges of necrotic lung lesions in NOS2-/-, RAG-/-, and C3HeB/FeJ, but were absent in wild-type mice. Both populations of Gr1(+)CD11b(+) cells expressed high levels of arginase-1, and IL-17, additional markers of myeloid derived suppressor cells. We then sorted the Gr1(hi) and Gr1(int) populations from M. tuberculosis infected NOS-/- mice and placed the sorted both Gr1(int) populations at different ratios with naïve or M. tuberculosis infected splenocytes and evaluated their ability to induce activation and proliferation of CD4+T cells. Our results showed that both Gr1(hi) and Gr1(int) cells were able to induce activation and proliferation of CD4+ T cells. However this response was reduced as the ratio of CD4(+) T to Gr1(+) cells increased. Our results illustrate a yet unrecognized interplay between Gr1(+) cells and CD4(+) T cells in tuberculosis.

Show MeSH
Related in: MedlinePlus