Limits...
Myeloid-Derived Suppressor Cells in Bacterial Infections.

Ost M, Singh A, Peschel A, Mehling R, Rieber N, Hartl D - Front Cell Infect Microbiol (2016)

Bottom Line: Myeloid-derived suppressor cells (MDSCs) comprise monocytic and granulocytic innate immune cells with the capability of suppressing T- and NK-cell responses.While the role of MDSCs has been studied in depth in malignant diseases, the understanding of their regulation and function in infectious disease conditions has just begun to evolve.Here we summarize and discuss the current view how MDSCs participate in bacterial infections and how this knowledge could be exploited for potential future therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Children's Hospital, University of Tübingen Tübingen, Germany.

ABSTRACT
Myeloid-derived suppressor cells (MDSCs) comprise monocytic and granulocytic innate immune cells with the capability of suppressing T- and NK-cell responses. While the role of MDSCs has been studied in depth in malignant diseases, the understanding of their regulation and function in infectious disease conditions has just begun to evolve. Here we summarize and discuss the current view how MDSCs participate in bacterial infections and how this knowledge could be exploited for potential future therapeutics.

No MeSH data available.


Related in: MedlinePlus

Signaling pathways involved in the expansion and activation of MDSCs. Induction/expansion and activation of MDSCs can be triggered through distinct pathways. Here, we provide an overview on different signaling molecules and pathways involved in these events. Bacterial infections either directly promote MDSC activation through microbial patterns (PAMPs), TLR ligation and NFκB-dependent pathways or indirectly through pro-inflammatory mediators, such as several interleukins and IFN-γ, that are secreted upon infection. Furthermore, S100 proteins are also involved in both of these processes.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4814452&req=5

Figure 1: Signaling pathways involved in the expansion and activation of MDSCs. Induction/expansion and activation of MDSCs can be triggered through distinct pathways. Here, we provide an overview on different signaling molecules and pathways involved in these events. Bacterial infections either directly promote MDSC activation through microbial patterns (PAMPs), TLR ligation and NFκB-dependent pathways or indirectly through pro-inflammatory mediators, such as several interleukins and IFN-γ, that are secreted upon infection. Furthermore, S100 proteins are also involved in both of these processes.

Mentions: Immature myeloid cells can be found in healthy individuals at low amounts in peripheral blood (Almand et al., 2001), which increase upon cancer, inflammation and infection. MDSC expansion and activation mechanisms depend on the MDSC phenotype and the species studied (Serafini, 2013; Condamine et al., 2015; Figure 1). MDSC expansion is mainly driven by STAT3, a transcription factor activated by GM-CSF, G-CSF, VEGF as well as IL-6 (Gabrilovich et al., 1998; Serafini et al., 2004; Song et al., 2005; Sawanobori et al., 2008), that influences cell proliferation and differentiation (Yu et al., 2009). Activated STAT3 also induces expression of S100A8 and A9 (Foell et al., 2007), which block differentiation of immature myeloid cells and lead to expansion of MDSCs (Cheng et al., 2008). In vivo inhibition of STAT3 via receptor tyrosine kinase inhibitor Sunitinib resulted in a lower amount of MDSCs (Xin et al., 2009). Other related transcription factors of the STAT family, particularly STAT1 and STAT6, also play a role in MDSC activation and function (Movahedi et al., 2008; Munera et al., 2010). STAT1 can be triggered by IFN-γ, whereas STAT6 response is initiated by IL-4 and IL-13 (Rutschman et al., 2001). Downstream, MDSC activation is primarily mediated by NFκB, which is triggered by pro-inflammatory mediators such as IL-1β and TNF-α (Tu et al., 2008; Hu et al., 2014) or toll-like receptor signaling via MyD88 (Delano et al., 2007). Furthermore, NFκB is involved in the ER stress response that is active in MDSCs (Condamine et al., 2014).


Myeloid-Derived Suppressor Cells in Bacterial Infections.

Ost M, Singh A, Peschel A, Mehling R, Rieber N, Hartl D - Front Cell Infect Microbiol (2016)

Signaling pathways involved in the expansion and activation of MDSCs. Induction/expansion and activation of MDSCs can be triggered through distinct pathways. Here, we provide an overview on different signaling molecules and pathways involved in these events. Bacterial infections either directly promote MDSC activation through microbial patterns (PAMPs), TLR ligation and NFκB-dependent pathways or indirectly through pro-inflammatory mediators, such as several interleukins and IFN-γ, that are secreted upon infection. Furthermore, S100 proteins are also involved in both of these processes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4814452&req=5

Figure 1: Signaling pathways involved in the expansion and activation of MDSCs. Induction/expansion and activation of MDSCs can be triggered through distinct pathways. Here, we provide an overview on different signaling molecules and pathways involved in these events. Bacterial infections either directly promote MDSC activation through microbial patterns (PAMPs), TLR ligation and NFκB-dependent pathways or indirectly through pro-inflammatory mediators, such as several interleukins and IFN-γ, that are secreted upon infection. Furthermore, S100 proteins are also involved in both of these processes.
Mentions: Immature myeloid cells can be found in healthy individuals at low amounts in peripheral blood (Almand et al., 2001), which increase upon cancer, inflammation and infection. MDSC expansion and activation mechanisms depend on the MDSC phenotype and the species studied (Serafini, 2013; Condamine et al., 2015; Figure 1). MDSC expansion is mainly driven by STAT3, a transcription factor activated by GM-CSF, G-CSF, VEGF as well as IL-6 (Gabrilovich et al., 1998; Serafini et al., 2004; Song et al., 2005; Sawanobori et al., 2008), that influences cell proliferation and differentiation (Yu et al., 2009). Activated STAT3 also induces expression of S100A8 and A9 (Foell et al., 2007), which block differentiation of immature myeloid cells and lead to expansion of MDSCs (Cheng et al., 2008). In vivo inhibition of STAT3 via receptor tyrosine kinase inhibitor Sunitinib resulted in a lower amount of MDSCs (Xin et al., 2009). Other related transcription factors of the STAT family, particularly STAT1 and STAT6, also play a role in MDSC activation and function (Movahedi et al., 2008; Munera et al., 2010). STAT1 can be triggered by IFN-γ, whereas STAT6 response is initiated by IL-4 and IL-13 (Rutschman et al., 2001). Downstream, MDSC activation is primarily mediated by NFκB, which is triggered by pro-inflammatory mediators such as IL-1β and TNF-α (Tu et al., 2008; Hu et al., 2014) or toll-like receptor signaling via MyD88 (Delano et al., 2007). Furthermore, NFκB is involved in the ER stress response that is active in MDSCs (Condamine et al., 2014).

Bottom Line: Myeloid-derived suppressor cells (MDSCs) comprise monocytic and granulocytic innate immune cells with the capability of suppressing T- and NK-cell responses.While the role of MDSCs has been studied in depth in malignant diseases, the understanding of their regulation and function in infectious disease conditions has just begun to evolve.Here we summarize and discuss the current view how MDSCs participate in bacterial infections and how this knowledge could be exploited for potential future therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Children's Hospital, University of Tübingen Tübingen, Germany.

ABSTRACT
Myeloid-derived suppressor cells (MDSCs) comprise monocytic and granulocytic innate immune cells with the capability of suppressing T- and NK-cell responses. While the role of MDSCs has been studied in depth in malignant diseases, the understanding of their regulation and function in infectious disease conditions has just begun to evolve. Here we summarize and discuss the current view how MDSCs participate in bacterial infections and how this knowledge could be exploited for potential future therapeutics.

No MeSH data available.


Related in: MedlinePlus