Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis

• Published in: Nature 2009-01, Vol.457 (7226), p.191-195
• Main Authors: Kim, Jiyun V, Dustin, Michael L, Kang, Silvia S, McGavern, Dorian B
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Biological and medical sciences; Blood-Brain Barrier - physiopathology; Cells; Central nervous system; Central Nervous System - blood supply; Central Nervous System - immunology; Central Nervous System - pathology; Central Nervous System - virology; Health aspects; Human viral diseases; Humanities and Social Sciences; Infections; Infectious diseases; letter; Lymphocytes; Lymphocytic choriomeningitis virus; Lymphocytic choriomeningitis virus - immunology; Lymphocytic choriomeningitis virus - pathogenicity; Medical sciences; Meninges - blood supply; Meninges - immunology; Meninges - pathology; Meninges - virology; Meningitis; Meningitis, Viral - immunology; Meningitis, Viral - pathology; Meningitis, Viral - physiopathology; Mice; Mice, Inbred C57BL; Monoclonal antibodies; Monocytes - cytology; Monocytes - immunology; multidisciplinary; Nervous system; Neural transmission; Neutrophil Infiltration; Neutrophils - cytology; Neutrophils - immunology; Pathology; Regulation; Science; Science (multidisciplinary); Seizures - immunology; Seizures - pathology; Seizures - physiopathology; Stromal Cells - virology; T cell proliferation; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - immunology; Viral diseases; Viral diseases of the nervous system; Viral meningitis
• ISSN: 0028-0836; 1476-4687; 1476-4679
• DOI: 10.1038/nature07591

Lymphocytic choriomeningitis virus infection of the mouse central nervous system (CNS) elicits fatal immunopathology through blood-brain barrier breakdown and convulsive seizures. Although lymphocytic-choriomeningitis-virus-specific cytotoxic T lymphocytes (CTLs) are essential for disease, their mechanism of action is not known. To gain insights into disease pathogenesis, we observed the dynamics of immune cells in the meninges by two-photon microscopy. Here we report visualization of motile CTLs and massive secondary recruitment of pathogenic monocytes and neutrophils that were required for vascular leakage and acute lethality. CTLs expressed multiple chemoattractants capable of recruiting myelomonocytic cells. We conclude that a CD8+ T-cell-dependent disorder can proceed in the absence of direct T-cell effector mechanisms and rely instead on CTL-recruited myelomonocytic cells.