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Infection and Immunity, March 2006, p. 1573-1579, Vol. 74, No. 3
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.3.1573-1579.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

CD40 Restrains In Vivo Growth of Toxoplasma gondii Independently of Gamma Interferon

Carlos S. Subauste* and Matthew Wessendarp

Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267

Received 16 August 2005/ Returned for modification 26 September 2005/ Accepted 12 December 2005

CD40-CD154 interaction is pivotal for resistance against numerous pathogens. However, it is not known if this pathway can also enhance in vivo resistance in gamma interferon (IFN-{gamma})-deficient hosts. This is an important question because patients and mice with defects in type 1 cytokine response can control a variety of pathogens. While blockade of endogenous CD154 resulted in a remarkable increase in parasite load in IFN-{gamma}–/– mice infected with Toxoplasma gondii, in vivo administration of a stimulatory anti-CD40 monoclonal antibody markedly reduced parasite load. This latter effect took place even in T-cell-depleted mice and was accompanied by induction of macrophage toxoplasmacidal activity. CD40 stimulation restricted T. gondii replication independently of STAT1, p47 GTPases, and nitric oxide. In vivo CD40 ligation enhanced tumor necrosis factor alpha (TNF-{alpha}) production by T. gondii-infected macrophages. In addition, CD40 stimulation required the presence of TNF receptor 2 to reduce parasite load in vivo. These results suggest that CD40-CD154 interaction regulates IFN-{gamma}-independent mechanisms of host protection through induction of macrophage antimicrobial activity and modulation of TNF-{alpha} signaling.

* Corresponding author. Mailing address: Department of Internal Medicine, University of Cincinnati College of Medicine, P.O. Box 670560, Cincinnati, OH 45267-0560. Phone: (513) 558-0562. Fax: (513) 558-2089. E-mail: carlos.subauste{at}uc.edu.

Editor: W. A. Petri, Jr.

Infection and Immunity, March 2006, p. 1573-1579, Vol. 74, No. 3
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.3.1573-1579.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Portillo, J.-A. C., Van Grol, J., Zheng, L., Okenka, G., Gentil, K., Garland, A., Carlson, E. C., Kern, T. S., Subauste, C. S. (2008). CD40 Mediates Retinal Inflammation and Neurovascular Degeneration. J. Immunol. 181: 8719-8726 [Abstract] [Full Text]  
  • Zhao, Y., Wilson, D., Matthews, S., Yap, G. S. (2007). Rapid Elimination of Toxoplasma gondii by Gamma Interferon-Primed Mouse Macrophages Is Independent of CD40 Signaling. Infect. Immun. 75: 4799-4803 [Abstract] [Full Text]  


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