Measles virus-induced immunosuppression: from effectors to mechanisms.
Immunosuppression is the major cause of infant death associated with acute measles. Hallmarks of this generalized modulation of immune functions include: (1) lymphopenia, (2) a prolonged cytokine imbalance consistent with suppression of cellular immunity to secondary infections and (3) silencing of peripheral blood lymphocytes that fail to expand in response to ex vivo stimulation. Lymphopenia results from depletion of T cells by mechanisms also involving MV infection, and expression of the major MV receptor CD150 plays an important role for targeting these cells. Virus transfer to T cells is thought to be mediated by dendritic cells (DCs), which are considered as central to the induction of T-cell silencing and functional skewing. MV interaction modulates functional differentiation of DCs, and thereby expression pattern of costimulatory molecules and soluble mediators. Moreover, MV proteins expressed by these cells actively silence T cells by interfering with signaling pathways essential for T-cell activation. As an essential component of this interference, the MV glycoprotein complex activates cellular sphingomyelinases in a contact-dependent manner, and these are effective at preventing stimulated rearrangements of the actin cytoskeleton and thereby morphological and functional polarization and motility of T cells.
Avota
Elita
E
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, Würzburg, Germany.
Gassert
Evelyn
E
Schneider-Schaulies
Sibylle
S
D015703:Antigens, CD / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion; D007108:Immune Tolerance; D008231:Lymphopenia / Q000276:immunology; D008457:Measles / Q000276:immunology* / Q000821:virology*; D008459:Measles virus / Q000276:immunology* / Q000472:pathogenicity*; D011956:Receptors, Cell Surface / Q000502:physiology; D011991:Receptors, Virus / Q000502:physiology; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000821:virology
D015703:Antigens, CD; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; C000604059:SLAMF1 protein, human; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1