Mice with neonatally induced inactivation of the vascular cell adhesion molecule-1 fail to control the parasite in Toxoplasma encephalitis.
Under various inflammatory conditions, cell adhesion molecules are up-regulated in the central nervous system (CNS) and may contribute to the recruitment of leukocytes to the brain. In the present study, the functional role of vascular cell adhesion molecule (VCAM)-1 in Toxoplasma encephalitis (TE) was addressed using VCAM(flox/flox MxCre) mice. Neonatal inactivation of the VCAM-1 gene resulted in a lack of induction of VCAM-1 on cerebral blood vessel endothelial cells, whereas the constitutive expression of VCAM-1 on choroid plexus epithelial cells and the ependyma was unaffected; in these animals, resistance to T. gondii was abolished, and VCAM(flox/flox MxCre) mice died of chronic TE caused by a failure to control parasites in the CNS. Although leukocyte recruitment to the CNS was unimpaired, the B cell response was significantly reduced as evidenced by reduced serum levels of anti-T. gondii-specific IgM and IgG antibodies. Furthermore, the frequency and activation state of intracerebral T. gondii-specific T cells were decreased, and microglial activation was markedly reduced. Taken together, these data demonstrate the crucial requirement of VCAM-1-mediated immune reactions for the control of an intracerebral infectious pathogen, whereas other cell adhesion molecules can efficiently compensate for VCAM-1-mediated homing across cerebral blood vessels.
Abteilung für Neuropathologie, Universität zu Köln, Cologne, Germany. neuropath@uni-koeln.de
Martina
M
Deckert
Sonja
S
Lütjen
Christoph E
CE
Leuker
Lai-Yu
LY
Kwok
Andreas
A
Strack
Werner
W
Müller
Norbert
N
Wagner
Dirk
D
Schlüter
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002908:Chronic Disease; D004660:Encephalitis / Q000276:immunology* / Q000469:parasitology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000469:parasitology; D016781:Toxoplasmosis, Cerebral / Q000276:immunology* / Q000469:parasitology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology*
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019010:Vascular Cell Adhesion Molecule-1; D007371:Interferon-gamma