This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hayashi, T.
Right arrow Articles by Catanzaro, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hayashi, T.
Right arrow Articles by Catanzaro, A.

 Previous Article  |  Next Article 

Infection and Immunity, July 1999, p. 3558-3565, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Role of CD40 Ligand in Mycobacterium avium Infection

Tomoko Hayashi, Savita P. Rao, Pascal R. Meylan, Richard S. Kornbluth, and Antonino Catanzaro*

Department of Medicine, University of California San Diego, San Diego, California

Received 29 January 1999/Returned for modification 2 March 1999/Accepted 14 April 1999

Mycobacterium avium is a common opportunistic pathogen in immunocompromised patients such as those infected with human immunodeficiency virus. Although M. avium is an intracellular organism replicating predominantly in macrophages, disseminated M. avium infection is seen in AIDS patients with CD4+ cell counts of <50 cells/µl, suggesting a possible involvement of a T cell-macrophage interaction for the elimination of M. avium. To determine whether CD40-CD40 ligand (CD40L) interactions play a role in M. avium infection, we studied the ability of CD40L to restrict M. avium replication in human monocyte-derived macrophages (MDM) in vitro. MDM were infected with M. avium and cocultured with CD40L-transfected 293 cells for 7 days. Intracellular growth of M. avium in these MDM was assessed by colony counting. CD40L-expressing cells inhibited growth of M. avium in MDM by 86.5% ± 4.2% compared to MDM cultured with control cells. These findings were verified by assays using purified, soluble recombinant human CD40L (CD40LT). CD40LT (5 µg/ml) inhibited intracellular growth of M. avium by 76.9% ± 18.0% compared to cells treated with medium alone. Inhibition by CD40LT was reduced by monoclonal antibodies (MAbs) against CD40 and CD40L. The inhibitory effect of CD40LT was not accompanied by enhancement of interleukin-12 (IL-12) production by M. avium-infected MDM, while CD40L-expressing cells stimulated IL-12 production by these cells. Treatment of M. avium-infected mice with MAb against murine CD40L resulted in recovery of larger numbers of organisms (0.8 to 1.0 log) from the spleens, livers, and lungs of these animals compared to infected mice which received normal immunoglobulin G. These results indicate that CD40-CD40L signaling may be an important step in host immune response against M. avium infection.

* Corresponding author. Mailing address: University of California San Diego Medical Center, 200 W. Arbor Dr., San Diego, CA 92103-8374. Phone (619) 543-5550. Fax: (619) 543-3276. E-mail: acatanzaro{at}ucsd.edu.

Infection and Immunity, July 1999, p. 3558-3565, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Miles, D. J. C., van der Sande, M., Crozier, S., Ojuola, O., Palmero, M. S., Sanneh, M., Touray, E. S., Rowland-Jones, S., Whittle, H., Ota, M., Marchant, A. (2008). Effects of Antenatal and Postnatal Environments on CD4 T-Cell Responses to Mycobacterium bovis BCG in Healthy Infants in The Gambia. CVI 15: 995-1002 [Abstract] [Full Text]  
  • Filipe-Santos, O., Bustamante, J., Haverkamp, M. H., Vinolo, E., Ku, C.-L., Puel, A., Frucht, D. M., Christel, K., von Bernuth, H., Jouanguy, E., Feinberg, J., Durandy, A., Senechal, B., Chapgier, A., Vogt, G., de Beaucoudrey, L., Fieschi, C., Picard, C., Garfa, M., Chemli, J., Bejaoui, M., Tsolia, M. N., Kutukculer, N., Plebani, A., Notarangelo, L., Bodemer, C., Geissmann, F., Israel, A., Veron, M., Knackstedt, M., Barbouche, R., Abel, L., Magdorf, K., Gendrel, D., Agou, F., Holland, S. M., Casanova, J.-L. (2006). X-linked susceptibility to mycobacteria is caused by mutations in NEMO impairing CD40-dependent IL-12 production. JEM 203: 1745-1759 [Abstract] [Full Text]  
  • Subauste, C. S., Wessendarp, M. (2006). CD40 Restrains In Vivo Growth of Toxoplasma gondii Independently of Gamma Interferon. Infect. Immun. 74: 1573-1579 [Abstract] [Full Text]  
  • Andrade, R. M., Wessendarp, M., Portillo, J.-A. C., Yang, J.-Q., Gomez, F. J., Durbin, J. E., Bishop, G. A., Subauste, C. S. (2005). TNF Receptor-Associated Factor 6-Dependent CD40 Signaling Primes Macrophages to Acquire Antimicrobial Activity in Response to TNF-{alpha}. J. Immunol. 175: 6014-6021 [Abstract] [Full Text]  
  • Andrade, R. M., Wessendarp, M., Subauste, C. S. (2003). CD154 Activates Macrophage Antimicrobial Activity in the Absence of IFN-{gamma} through a TNF-{alpha}-Dependent Mechanism. J. Immunol. 171: 6750-6756 [Abstract] [Full Text]  
  • Majorov, K. B., Lyadova, I. V., Kondratieva, T. K., Eruslanov, E. B., Rubakova, E. I., Orlova, M. O., Mischenko, V. V., Apt, A. S. (2003). Different Innate Ability of I/St and A/Sn Mice To Combat Virulent Mycobacterium tuberculosis: Phenotypes Expressed in Lung and Extrapulmonary Macrophages. Infect. Immun. 71: 697-707 [Abstract] [Full Text]  
  • Larkin, R., Benjamin, C. D., Hsu, Y.-M., Li, Q., Zukowski, L., Silver, R. F. (2002). CD40 Ligand (CD154) Does Not Contribute to Lymphocyte-Mediated Inhibition of Virulent Mycobacterium tuberculosis within Human Monocytes. Infect. Immun. 70: 4716-4720 [Abstract] [Full Text]  
  • Hayashi, T., Rao, S. P., Takabayashi, K., Van Uden, J. H., Kornbluth, R. S., Baird, S. M., Taylor, M. W., Carson, D. A., Catanzaro, A., Raz, E. (2001). Enhancement of Innate Immunity against Mycobacterium avium Infection by Immunostimulatory DNA Is Mediated by Indoleamine 2,3-Dioxygenase. Infect. Immun. 69: 6156-6164 [Abstract] [Full Text]  
  • Hogan, L. H., Markofski, W., Bock, A., Barger, B., Morrissey, J. D., Sandor, M. (2001). Mycobacterium bovis BCG-Induced Granuloma Formation Depends on Gamma Interferon and CD40 Ligand but Does Not Require CD28. Infect. Immun. 69: 2596-2603 [Abstract] [Full Text]  
  • Kornbluth, R. S. (2000). The emerging role of CD40 ligand in HIV infection. J. Leukoc. Biol. 68: 373-382 [Abstract] [Full Text]  
  • Samten, B., Thomas, E. K., Gong, J., Barnes, P. F. (2000). Depressed CD40 Ligand Expression Contributes to Reduced Gamma Interferon Production in Human Tuberculosis. Infect. Immun. 68: 3002-3006 [Abstract] [Full Text]  
  • Hwang, Y.-i., Nahm, M. H., Briles, D. E., Thomas, D., Purkerson, J. M. (2000). Acquired, but Not Innate, Immune Responses to Streptococcus pneumoniae Are Compromised by Neutralization of CD40L. Infect. Immun. 68: 511-517 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»