The role of myeloid-derived suppressor cells in chronic infectious diseases and the current methodology available for their study

Peñaloza, Hernán F.; Álvarez, Diana; Muñoz‐Durango, Natalia; Schultz, Bárbara M.; González, Pablo A.; Kalergis, Alexis M.; Bueno, Susan M.

doi:10.1002/jlb.mr0618-233r

Cited by 27 publications

(25 citation statements)

References 147 publications

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“…In addition to mature neutrophils, under pathogenic conditions such as chronic inflammatory disease and cancer, immature myeloid cells, known as myeloid-derived suppressor cells (MDSCs), are recruited from the bone marrow prior to terminal differentiation [85,108]. Granulocytic MDSCs (G-MDSCs) are thought to be immature neutrophils since they morphologically and phenotypically resemble neutrophils.…”

Section: Tumour-associated Neutrophilsmentioning

confidence: 99%

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Elliot

Myllymäki

Feng

2020

Cells

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The zebrafish is now an important model organism for cancer biology studies and provides unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level, providing novel insights into our understanding of cancer. Here we summarise the available transgenic zebrafish tumour models and discuss what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response towards transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour-associated macrophages and neutrophils in mammalian models and present evidence that supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to the signals that mediate leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells in zebrafish appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

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Section: Tumour-associated Neutrophilsmentioning

confidence: 99%

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Elliot

Myllymäki

Feng

2020

Cells

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“…In response to bacterial infection, MDSC recruitment and activity are typically associated with resolution and/or chronicity (28). This has been described during pulmonary infections caused by Pseudomonas aeruginosa (28) and nonpulmonary infections with major pathogens such as Staphylococcus aureus, Salmonella enterica, and Porphyromonas gingivalis (10,13,14,(29)(30)(31)(32)(33)(34). In each of these cases, recruited MDSCs inhibit the innate and adaptive immune responses, causing chronic infection.…”

Section: Figmentioning

confidence: 99%

“…Finally, even though the transfer of non-IL-10-producing BM-MDSCs did not have an effect on bacterial clearance and lung inflammation, it had a positive impact on host survival by either delaying host mortality or improving host survival from 0% to 25%. It has been reported that BM-MDSCs can efficiently suppress T cell activation through the activity of arginase-1, iNOS, Cox2, vascular endothelial growth factor (VEGF), Ido1, and other factors (28). It is highly possible that these molecules also have an important role in the modulation of the inflammatory response during KP35 infection; however, more studies are needed to establish the real contribution and the mechanisms involved.…”

Section: Figmentioning

confidence: 99%

Interleukin-10 Produced by Myeloid-Derived Suppressor Cells Provides Protection to Carbapenem-ResistantKlebsiella pneumoniaeSequence Type 258 by Enhancing Its Clearance in the Airways

et al. 2019

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Carbapenem-resistant Klebsiella pneumoniae sequence type 258 (CRKP-ST258) can cause chronic infections in lungs and airways, with repeated episodes of bacteremia. In this report we addressed whether the recruitment of myeloid cells producing the anti-inflammatory cytokine interleukin-10 (IL-10) modulates the clearance of CKRP-ST258 in the lungs and establishes bacterial persistence. Our data demonstrate that during pneumonia caused by a clinical isolate of CRKP-ST258 (KP35) there is an early recruitment of monocyte-myeloid-derived suppressor cells (M-MDSCs) and neutrophils that actively produce IL-10. However, M-MDSCs were the cells that sustained the production of IL-10 over the time of infection evaluated. Using mice unable to produce IL-10 (IL-10 Ϫ/Ϫ ), we observed that the production of this cytokine during the infection caused by KP35 is important to control bacterial burden, to prevent lung damage, to modulate cytokine production, and to improve host survival. Importantly, intranasal transfer of bone marrow-derived M-MDSCs from mice able to produce IL-10 at 1 day prior to infection improved the ability of IL-10 Ϫ/Ϫ mice to clear KP35 in the lungs, decreasing their mortality. Altogether, our data demonstrate that IL-10 produced by M-MDSCs is required for bacterial clearance, reduction of lung tissue damage, and host survival during KP35 pneumonia.

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“…In addition to mature neutrophils, under pathogenic conditions such as chronic inflammatory disease and cancer, immature myeloid cells, known as myeloid-derived suppressor cells (MDSCs), are recruited from the bone marrow prior to terminal differentiation [68,90]. Granulocytic MDSCs (G-MDSCs) are thought to be immature neutrophils since they morphologically and phenotypically resemble neutrophils.…”

Section: Tumour Associated Neutrophilsmentioning

confidence: 99%

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Elliot

Myllymäki

Feng

2020

Preprint

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The zebrafish is now an important model organism for cancer biology studies and provides some unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level thus providing novel insights into our understanding of cancer. Here we summarise and discuss available transgenic zebrafish tumour models and what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response toward transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour associated macrophages and neutrophils in mammalian models and present evidence which supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to signals mediating leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

show abstract

The role of myeloid-derived suppressor cells in chronic infectious diseases and the current methodology available for their study

Cited by 27 publications

References 147 publications

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Interleukin-10 Produced by Myeloid-Derived Suppressor Cells Provides Protection to Carbapenem-ResistantKlebsiella pneumoniaeSequence Type 258 by Enhancing Its Clearance in the Airways

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

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