Limits...
Pathologic and Protective Roles for Microglial Subsets and Bone Marrow- and Blood-Derived Myeloid Cells in Central Nervous System Inflammation.

Wlodarczyk A, Cédile O, Jensen KN, Jasson A, Mony JT, Khorooshi R, Owens T - Front Immunol (2015)

Bottom Line: However, as in other tissues, neuroinflammation can have beneficial as well as pathological outcomes.Moreover, in contrast to BMDM/DC, both subsets of microglia express protective interferon-beta (IFNβ), high levels of colony-stimulating factor-1 receptor, and do not express the Th1-associated transcription factor T-bet.Taken together, our data suggest that CD11c(+) microglia, CD11c(-) microglia, and infiltrating BMDM/DC represent separate and distinct populations and illustrate the heterogeneity of the CNS inflammatory environment.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology Research, Institute for Molecular Medicine, University of Southern Denmark , Odense , Denmark.

ABSTRACT
Inflammation is a series of processes designed for eventual clearance of pathogens and repair of damaged tissue. In the context of autoimmune recognition, inflammatory processes are usually considered to be pathological. This is also true for inflammatory responses in the central nervous system (CNS). However, as in other tissues, neuroinflammation can have beneficial as well as pathological outcomes. The complex role of encephalitogenic T cells in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) may derive from heterogeneity of the myeloid cells with which these T cells interact within the CNS. Myeloid cells, including resident microglia and infiltrating bone marrow-derived cells, such as dendritic cells (DC) and monocytes/macrophages [bone marrow-derived macrophages (BMDM)], are highly heterogeneous populations that may be involved in neurotoxicity and also immunoregulation and regenerative processes. Better understanding and characterization of myeloid cell heterogeneity is essential for future development of treatments controlling inflammation and inducing neuroprotection and neuroregeneration in diseased CNS. Here, we describe and compare three populations of myeloid cells: CD11c(+) microglia, CD11c(-) microglia, and CD11c(+) blood-derived cells in terms of their pathological versus protective functions in the CNS of mice with EAE. Our data show that CNS-resident microglia include functionally distinct subsets that can be distinguished by their expression of CD11c. These subsets differ in their expression of Arg-1, YM1, iNOS, IL-10, and IGF-1. Moreover, in contrast to BMDM/DC, both subsets of microglia express protective interferon-beta (IFNβ), high levels of colony-stimulating factor-1 receptor, and do not express the Th1-associated transcription factor T-bet. Taken together, our data suggest that CD11c(+) microglia, CD11c(-) microglia, and infiltrating BMDM/DC represent separate and distinct populations and illustrate the heterogeneity of the CNS inflammatory environment.

No MeSH data available.


Related in: MedlinePlus

Comparison of expression of M1/M2-associated genes in myeloid cells in CNS in EAE. Expression of ARG1, YM1, iNOS, IL-10, and IGF-1 in fluorescence-activated cell sorted CD11c+ microglia and CD11c− microglia and CD45highCD11c+ infiltrating cells (BMDM/DC) from the central nervous system from mice with severe EAE were analyzed by quantitative real-time PCR. Data are presented as means ± SEM of three individual experiments (n ≥ 5, where n represents a pool of 2–3 individual mice); *P < 0.05; **P < 0.01.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4562247&req=5

Figure 5: Comparison of expression of M1/M2-associated genes in myeloid cells in CNS in EAE. Expression of ARG1, YM1, iNOS, IL-10, and IGF-1 in fluorescence-activated cell sorted CD11c+ microglia and CD11c− microglia and CD45highCD11c+ infiltrating cells (BMDM/DC) from the central nervous system from mice with severe EAE were analyzed by quantitative real-time PCR. Data are presented as means ± SEM of three individual experiments (n ≥ 5, where n represents a pool of 2–3 individual mice); *P < 0.05; **P < 0.01.

Mentions: We were further interested in differences between microglia and blood-derived myeloid cells; thus, we compared mRNA levels of ARG1, YM1, iNOS, IL-10, and IGF1 between microglia populations and CD45highCD11c+ cells (BMDM/DC). Here, we show that BMDM/DC express significantly higher levels of ARG1, iNOS, and IL-10 than both populations of microglia, they also expressed significantly more transcripts of YM1 than CD11c+ microglia, but less than CD11c− microglia (Figure 5). Interestingly, while CD11c+ microglia showed high expression of IGF1 transcripts, neither CD11c− microglia nor infiltrating CD45high cells expressed significant levels of this growth factor (Figure 5). Association of IGF1 expression with CD11c+ microglia has also been reported in glatiramer acetate-treated transgenic mice with an AD-like phenotype and has been suggested as a mechanistic basis for the ability of CD11c+ microglia to promote neurogenesis (34).


Pathologic and Protective Roles for Microglial Subsets and Bone Marrow- and Blood-Derived Myeloid Cells in Central Nervous System Inflammation.

Wlodarczyk A, Cédile O, Jensen KN, Jasson A, Mony JT, Khorooshi R, Owens T - Front Immunol (2015)

Comparison of expression of M1/M2-associated genes in myeloid cells in CNS in EAE. Expression of ARG1, YM1, iNOS, IL-10, and IGF-1 in fluorescence-activated cell sorted CD11c+ microglia and CD11c− microglia and CD45highCD11c+ infiltrating cells (BMDM/DC) from the central nervous system from mice with severe EAE were analyzed by quantitative real-time PCR. Data are presented as means ± SEM of three individual experiments (n ≥ 5, where n represents a pool of 2–3 individual mice); *P < 0.05; **P < 0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562247&req=5

Figure 5: Comparison of expression of M1/M2-associated genes in myeloid cells in CNS in EAE. Expression of ARG1, YM1, iNOS, IL-10, and IGF-1 in fluorescence-activated cell sorted CD11c+ microglia and CD11c− microglia and CD45highCD11c+ infiltrating cells (BMDM/DC) from the central nervous system from mice with severe EAE were analyzed by quantitative real-time PCR. Data are presented as means ± SEM of three individual experiments (n ≥ 5, where n represents a pool of 2–3 individual mice); *P < 0.05; **P < 0.01.
Mentions: We were further interested in differences between microglia and blood-derived myeloid cells; thus, we compared mRNA levels of ARG1, YM1, iNOS, IL-10, and IGF1 between microglia populations and CD45highCD11c+ cells (BMDM/DC). Here, we show that BMDM/DC express significantly higher levels of ARG1, iNOS, and IL-10 than both populations of microglia, they also expressed significantly more transcripts of YM1 than CD11c+ microglia, but less than CD11c− microglia (Figure 5). Interestingly, while CD11c+ microglia showed high expression of IGF1 transcripts, neither CD11c− microglia nor infiltrating CD45high cells expressed significant levels of this growth factor (Figure 5). Association of IGF1 expression with CD11c+ microglia has also been reported in glatiramer acetate-treated transgenic mice with an AD-like phenotype and has been suggested as a mechanistic basis for the ability of CD11c+ microglia to promote neurogenesis (34).

Bottom Line: However, as in other tissues, neuroinflammation can have beneficial as well as pathological outcomes.Moreover, in contrast to BMDM/DC, both subsets of microglia express protective interferon-beta (IFNβ), high levels of colony-stimulating factor-1 receptor, and do not express the Th1-associated transcription factor T-bet.Taken together, our data suggest that CD11c(+) microglia, CD11c(-) microglia, and infiltrating BMDM/DC represent separate and distinct populations and illustrate the heterogeneity of the CNS inflammatory environment.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology Research, Institute for Molecular Medicine, University of Southern Denmark , Odense , Denmark.

ABSTRACT
Inflammation is a series of processes designed for eventual clearance of pathogens and repair of damaged tissue. In the context of autoimmune recognition, inflammatory processes are usually considered to be pathological. This is also true for inflammatory responses in the central nervous system (CNS). However, as in other tissues, neuroinflammation can have beneficial as well as pathological outcomes. The complex role of encephalitogenic T cells in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) may derive from heterogeneity of the myeloid cells with which these T cells interact within the CNS. Myeloid cells, including resident microglia and infiltrating bone marrow-derived cells, such as dendritic cells (DC) and monocytes/macrophages [bone marrow-derived macrophages (BMDM)], are highly heterogeneous populations that may be involved in neurotoxicity and also immunoregulation and regenerative processes. Better understanding and characterization of myeloid cell heterogeneity is essential for future development of treatments controlling inflammation and inducing neuroprotection and neuroregeneration in diseased CNS. Here, we describe and compare three populations of myeloid cells: CD11c(+) microglia, CD11c(-) microglia, and CD11c(+) blood-derived cells in terms of their pathological versus protective functions in the CNS of mice with EAE. Our data show that CNS-resident microglia include functionally distinct subsets that can be distinguished by their expression of CD11c. These subsets differ in their expression of Arg-1, YM1, iNOS, IL-10, and IGF-1. Moreover, in contrast to BMDM/DC, both subsets of microglia express protective interferon-beta (IFNβ), high levels of colony-stimulating factor-1 receptor, and do not express the Th1-associated transcription factor T-bet. Taken together, our data suggest that CD11c(+) microglia, CD11c(-) microglia, and infiltrating BMDM/DC represent separate and distinct populations and illustrate the heterogeneity of the CNS inflammatory environment.

No MeSH data available.


Related in: MedlinePlus