Experimental autoimmune encephalomyelitis (EAE) in CCR2(-/-) mice: susceptibility in multiple strains

Area of Science:

• Immunology
• Neuroscience
• Molecular Biology

Background:

• Chemokines and their receptors (CCR) guide immune cells to inflammation sites.
• CCR2 on monocytes is thought to be crucial for central nervous system (CNS) infiltration in experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model.
• Previous studies suggested CCR2-deficient (CCR2(-/-)) mice are resistant to EAE.

Purpose of the Study:

• To investigate the susceptibility of different CCR2(-/-) mouse strains to EAE.
• To analyze the cellular infiltrate and compensatory immune mechanisms in CCR2(-/-) mice during EAE.

Main Methods:

• Evaluation of EAE susceptibility in three CCR2(-/-) mouse strains (C57BL/6 x J129, Balb c, C57BL/6).
• Neuropathological examination of CNS lesions.
• Analysis of gene expression using RNase protection assay and in situ hybridization.
• In vitro assays to assess immune cell function.

Main Results:

• All three CCR2(-/-) mouse strains exhibited susceptibility to EAE (100% for C57BL/6 x J129 and Balb c; 67% for C57BL/6).
• CNS lesions in CCR2(-/-) mice showed an increased presence of neutrophils, unlike the monocyte abundance in wild-type animals.
• Increased mRNA levels for alternative chemokines and CCRs indicated compensatory immune responses.
• Neutrophil infiltration led to demyelination, confirming disease progression.

Conclusions:

• Deletion of CCR2 does not prevent EAE development.
• Immune system compensates for CCR2 deficiency through neutrophil recruitment and alternative chemokine pathways.
• Chemokine receptor promiscuity can overcome specific receptor deficits, allowing autoimmune disease manifestation.