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Immune responses to non-tumor antigens in the central nervous system.

Huber AK, Duncker PC, Irani DN - Front Oncol (2014)

Bottom Line: The central nervous system (CNS), once viewed as an immune-privileged site protected by the blood-brain barrier (BBB), is now known to be a dynamic immunological environment through which immune cells migrate to prevent and respond to events such as localized infection.During these responses, endogenous glial cells, including astrocytes and microglia, become highly reactive and may secrete inflammatory mediators that regulate BBB permeability and recruit additional circulating immune cells.Here, we discuss the various roles played by astrocytes, microglia, and infiltrating immune cells during host immunity to non-tumor antigens in the CNS, focusing first on bacterial and viral infections, and then turning to responses directed against self-antigens in the setting of CNS autoimmunity.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Michigan Medical School , Ann Arbor, MI , USA.

ABSTRACT
The central nervous system (CNS), once viewed as an immune-privileged site protected by the blood-brain barrier (BBB), is now known to be a dynamic immunological environment through which immune cells migrate to prevent and respond to events such as localized infection. During these responses, endogenous glial cells, including astrocytes and microglia, become highly reactive and may secrete inflammatory mediators that regulate BBB permeability and recruit additional circulating immune cells. Here, we discuss the various roles played by astrocytes, microglia, and infiltrating immune cells during host immunity to non-tumor antigens in the CNS, focusing first on bacterial and viral infections, and then turning to responses directed against self-antigens in the setting of CNS autoimmunity.

No MeSH data available.


Related in: MedlinePlus

Orchestration of the immune response during bacterial infection of the CNS. In the quiescent CNS (1), bacteria typically gain entry by transcytosis across the endothelial cells of the BBB, or by passing in between endothelial cells where tight junctions have been disrupted (2). Common bacterial motifs (PAMPs) are recognized by pattern recognition receptors (PRRs) on microglia and astrocytes resulting in their activation. This causes changes in glial cell morphology, enhanced production of inflammatory mediators that recruit neutrophils, monocytes, and T cells, and increased endothelial cell expression of adhesion molecules, including ICAM-1 and VCAM-1 (3). Circulating neutrophils, monocytes, and T cells then bind and extravasate into the infected CNS (4). Neutrophils directly phagocytize and kill bacteria through the release of defensins, lytic enzymes, and anti-microbial peptides (5). Neutrophils also produce MMPs, IL-6, IL-8, CXCL9, and CXCL10 that further open the BBB and shift the chemotactic profile toward the recruitment of T cells. Bacterial antigens are presented to T cells by microglia and/or infiltrating monocytes, transitioning from innate immunity toward an adaptive immune response (6). Resolution of bacterial infection returns tight junctions to normal and microglia and astrocytes to a resting state (7).
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Figure 1: Orchestration of the immune response during bacterial infection of the CNS. In the quiescent CNS (1), bacteria typically gain entry by transcytosis across the endothelial cells of the BBB, or by passing in between endothelial cells where tight junctions have been disrupted (2). Common bacterial motifs (PAMPs) are recognized by pattern recognition receptors (PRRs) on microglia and astrocytes resulting in their activation. This causes changes in glial cell morphology, enhanced production of inflammatory mediators that recruit neutrophils, monocytes, and T cells, and increased endothelial cell expression of adhesion molecules, including ICAM-1 and VCAM-1 (3). Circulating neutrophils, monocytes, and T cells then bind and extravasate into the infected CNS (4). Neutrophils directly phagocytize and kill bacteria through the release of defensins, lytic enzymes, and anti-microbial peptides (5). Neutrophils also produce MMPs, IL-6, IL-8, CXCL9, and CXCL10 that further open the BBB and shift the chemotactic profile toward the recruitment of T cells. Bacterial antigens are presented to T cells by microglia and/or infiltrating monocytes, transitioning from innate immunity toward an adaptive immune response (6). Resolution of bacterial infection returns tight junctions to normal and microglia and astrocytes to a resting state (7).

Mentions: Bacterial infections of the CNS are rare, but often life threatening, events (76). Excluding direct inoculation following CNS trauma, bacteria typically gain CNS entry following hematogenous dissemination from distant sites (lungs and heart valves) or by direct extension from parameningeal foci of infection (inner ear and sinuses). Penetration of the BBB may occur via three potential mechanisms: (1) direct destruction of capillary ECs (77, 78), (2) disruption of intercellular TJ and migration in between ECs (79), and (3) transcytosis via intracellular vesicles directly through ECs (80). Once inside, numerous innate immune receptors and pathways are activated (Figure 1).


Immune responses to non-tumor antigens in the central nervous system.

Huber AK, Duncker PC, Irani DN - Front Oncol (2014)

Orchestration of the immune response during bacterial infection of the CNS. In the quiescent CNS (1), bacteria typically gain entry by transcytosis across the endothelial cells of the BBB, or by passing in between endothelial cells where tight junctions have been disrupted (2). Common bacterial motifs (PAMPs) are recognized by pattern recognition receptors (PRRs) on microglia and astrocytes resulting in their activation. This causes changes in glial cell morphology, enhanced production of inflammatory mediators that recruit neutrophils, monocytes, and T cells, and increased endothelial cell expression of adhesion molecules, including ICAM-1 and VCAM-1 (3). Circulating neutrophils, monocytes, and T cells then bind and extravasate into the infected CNS (4). Neutrophils directly phagocytize and kill bacteria through the release of defensins, lytic enzymes, and anti-microbial peptides (5). Neutrophils also produce MMPs, IL-6, IL-8, CXCL9, and CXCL10 that further open the BBB and shift the chemotactic profile toward the recruitment of T cells. Bacterial antigens are presented to T cells by microglia and/or infiltrating monocytes, transitioning from innate immunity toward an adaptive immune response (6). Resolution of bacterial infection returns tight junctions to normal and microglia and astrocytes to a resting state (7).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230036&req=5

Figure 1: Orchestration of the immune response during bacterial infection of the CNS. In the quiescent CNS (1), bacteria typically gain entry by transcytosis across the endothelial cells of the BBB, or by passing in between endothelial cells where tight junctions have been disrupted (2). Common bacterial motifs (PAMPs) are recognized by pattern recognition receptors (PRRs) on microglia and astrocytes resulting in their activation. This causes changes in glial cell morphology, enhanced production of inflammatory mediators that recruit neutrophils, monocytes, and T cells, and increased endothelial cell expression of adhesion molecules, including ICAM-1 and VCAM-1 (3). Circulating neutrophils, monocytes, and T cells then bind and extravasate into the infected CNS (4). Neutrophils directly phagocytize and kill bacteria through the release of defensins, lytic enzymes, and anti-microbial peptides (5). Neutrophils also produce MMPs, IL-6, IL-8, CXCL9, and CXCL10 that further open the BBB and shift the chemotactic profile toward the recruitment of T cells. Bacterial antigens are presented to T cells by microglia and/or infiltrating monocytes, transitioning from innate immunity toward an adaptive immune response (6). Resolution of bacterial infection returns tight junctions to normal and microglia and astrocytes to a resting state (7).
Mentions: Bacterial infections of the CNS are rare, but often life threatening, events (76). Excluding direct inoculation following CNS trauma, bacteria typically gain CNS entry following hematogenous dissemination from distant sites (lungs and heart valves) or by direct extension from parameningeal foci of infection (inner ear and sinuses). Penetration of the BBB may occur via three potential mechanisms: (1) direct destruction of capillary ECs (77, 78), (2) disruption of intercellular TJ and migration in between ECs (79), and (3) transcytosis via intracellular vesicles directly through ECs (80). Once inside, numerous innate immune receptors and pathways are activated (Figure 1).

Bottom Line: The central nervous system (CNS), once viewed as an immune-privileged site protected by the blood-brain barrier (BBB), is now known to be a dynamic immunological environment through which immune cells migrate to prevent and respond to events such as localized infection.During these responses, endogenous glial cells, including astrocytes and microglia, become highly reactive and may secrete inflammatory mediators that regulate BBB permeability and recruit additional circulating immune cells.Here, we discuss the various roles played by astrocytes, microglia, and infiltrating immune cells during host immunity to non-tumor antigens in the CNS, focusing first on bacterial and viral infections, and then turning to responses directed against self-antigens in the setting of CNS autoimmunity.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Michigan Medical School , Ann Arbor, MI , USA.

ABSTRACT
The central nervous system (CNS), once viewed as an immune-privileged site protected by the blood-brain barrier (BBB), is now known to be a dynamic immunological environment through which immune cells migrate to prevent and respond to events such as localized infection. During these responses, endogenous glial cells, including astrocytes and microglia, become highly reactive and may secrete inflammatory mediators that regulate BBB permeability and recruit additional circulating immune cells. Here, we discuss the various roles played by astrocytes, microglia, and infiltrating immune cells during host immunity to non-tumor antigens in the CNS, focusing first on bacterial and viral infections, and then turning to responses directed against self-antigens in the setting of CNS autoimmunity.

No MeSH data available.


Related in: MedlinePlus