Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice

PNAS, 2009 · DOI: 10.1073/pnas.0911405106 · Published: December 8, 2009

Simple Explanation

The study investigates the role of the immune system in the peripheral nervous system (PNS) of mice with a genetic mutation that mimics ALS. The researchers found that immune cells, specifically macrophages, are activated in the PNS of these mice, even before the onset of symptoms. Antibodies and complement proteins, which are part of the humoral immune system, were also found in the PNS tissue, suggesting a combined immune response.

Study Duration

Not specified

Participants

mSOD1G93A and SOD1G37R transgenic mouse models of ALS

Evidence Level

Not specified

Key Findings

1
Macrophages are activated throughout the PNS in mutant SOD1G93A and SOD1G37R transgenic mouse models of ALS.
2
Macrophage activation occurs pre-symptomatically, expanding from focal arrays within nerve bundles to a tissue-wide distribution after symptom onset.
3
Humoral antibodies and complement localize to PNS tissue in tandem with macrophage recruitment, and deficiency in complement C4 leads to decreased macrophage activation.

Research Summary

This study characterizes a system-wide infiltration of macrophages in the PNS of mutant SOD1 mice that accompanies axon degeneration in ventral roots, sciatic nerves, and muscle tissues. The origin and nature of CNS myeloid cells are distinct from PNS myeloid cells in ALS. Microglia in mutant SOD1 mice are primarily tissue resident cells, whereas PNS macrophages are mainly derived from the circulation. Progressively increased innate and humoral activation was found in the PNS of mutant SOD1 mice. Activation of the immune system is intimately connected with the process of motor neuron degeneration.

Practical Implications

Therapeutic Targeting

The immunopathology occurring in the PNS offers a more accessible target for therapeutic modulation, as the blood-nerve barrier is relatively permeable to therapeutic agents and antibodies.

Understanding Disease Mechanisms

Further analysis of neuroimmune communication may lead to targeted treatments to extend motor neuron survival in ALS.

Combined Therapies

Modulating both innate and humoral immunity in the PNS could potentially slow down ALS progression.

Study Limitations

1
The study is limited to mouse models of ALS, and findings may not directly translate to human patients.
2
The specific peripheral nerve antigens recognized by natural antibodies in ALS are not identified.
3
Compensatory molecular pathways that may mitigate the effects of C4 deficiency on immune activation and macrophage recruitment were not fully explored.

Your Feedback

Was this summary helpful?

Back to Immunology