The CD40/CD40 ligand interaction is required for resistance to toxoplasmic encephalitis.
Since the CD40/CD40 ligand (CD40L) interaction is involved in the regulation of macrophage production of interleukin 12 (IL-12) and T-cell production of gamma interferon (IFN-gamma), effector cell functions associated with resistance to Toxoplasma gondii, the role of CD40L in immunity to this parasite was assessed. Infection of C57BL/6 mice with T. gondii results in an upregulation of CD40 expression on accessory cell populations at local sites of infection as well as in lymphoid tissues. Splenocytes from C57BL/6 mice infected with T. gondii for 5 days produced high levels of IL-12 and IFN-gamma when stimulated with toxoplasma lysate antigen, and blocking CD40L did not significantly alter the production of IFN-gamma or IL-12 by these cells. Similar results were observed with splenocytes and mononuclear cells isolated from the brains of chronically infected mice. Interestingly, although CD40L(-/-) mice infected with T. gondii produced less IL-12 than wild-type mice, they produced comparable levels of IFN-gamma but succumbed to toxoplasmic encephalitis 4 to 5 weeks after infection. The inability of CD40L(-/-) mice to control parasite replication in the brain correlated with the ability of soluble CD40L, in combination with IFN-gamma, to activate macrophages in vitro to control replication of T. gondii. Together, these results identify an important role for the CD40/CD40L interaction in resistance to T. gondii. However, this interaction may be more important in the control of parasite replication in the brain rather than the generation of protective T-cell responses during toxoplasmosis.
Reichmann
G
G
Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6050, USA.
Walker
W
W
Villegas
E N
EN
Craig
L
L
Cai
G
G
Alexander
J
J
Hunter
C A
CA
D000818:Animals; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D004660:Encephalitis / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008264:Macrophages / Q000469:parasitology / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008808:Mice, Inbred CBA; D009569:Nitric Oxide / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology; D016781:Toxoplasmosis, Cerebral / Q000276:immunology*
D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma