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 Nau, G. J.
Right arrow Articles by Young, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nau, G. J.
Right arrow Articles by Young, R. A.

 Previous Article  |  Next Article 

Infection and Immunity, August 1999, p. 4223-4230, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Attenuated Host Resistance against Mycobacterium bovis BCG Infection in Mice Lacking Osteopontin

Gerard J. Nau,1,2 Lucy Liaw,3,dagger Geoffrey L. Chupp,4,Dagger Jeffrey S. Berman,4,5 Brigid L. M. Hogan,3 and Richard A. Young1,*

Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 021421; Infectious Disease Unit, Massachusetts General Hospital, Boston, Massachusetts 021142; Howard Hughes Medical Institute and Department of Cell Biology, Vanderbilt University Medical Center, Nashville, Tennessee 372323; Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 021884; and Boston VA Medical Center, Boston, Massachusetts 021305

Received 24 February 1999/Returned for modification 14 April 1999/Accepted 22 April 1999

Expression of the cytokine osteopontin (OPN) is elevated in granulomas caused by Mycobacterium tuberculosis. We tested the hypothesis that OPN contributes to host protection in a mouse model of mycobacterial infection. When infected with Mycobacterium bovis BCG, mice lacking a functional OPN gene had more severe infections characterized by heavier bacterial loads and a delayed clearance of the bacteria. The OPN-null mice had greater granuloma burdens consistent with the elevated bacterial load. The ability of osteopontin to facilitate the clearance of mycobacteria was most pronounced early after infection and appeared to be independent of known mediators of resistance to infection by mycobacteria: antigen-specific T-cell immunity, gamma interferon production, and nitric oxide production. BCG grew more rapidly in macrophages derived from OPN-null mice than in those from wild-type mice, demonstrating that the null phenotype was due to an intrinsic macrophage defect. These results indicate that osteopontin augments the host response against a mycobacterial infection and that it acts independently from other antimycobacterial resistance mechanisms.

* Corresponding author. Mailing address: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142. Phone: (617) 258-5218. Fax: (617) 258-0376. E-mail: young{at}wi.mit.edu.

dagger Present address: Center for Molecular Medicine, Maine Medical Center Research Institute, South Portland, ME 04106.

Dagger Present address: Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT 06520.

Infection and Immunity, August 1999, p. 4223-4230, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Schack, L., Lange, A., Kelsen, J., Agnholt, J., Christensen, B., Petersen, T. E., Sorensen, E. S. (2009). Considerable variation in the concentration of osteopontin in human milk, bovine milk, and infant formulas. J DAIRY SCI 92: 5378-5385 [Abstract] [Full Text]  
  • Schack, L., Stapulionis, R., Christensen, B., Kofod-Olsen, E., Skov Sorensen, U. B., Vorup-Jensen, T., Sorensen, E. S., Hollsberg, P. (2009). Osteopontin Enhances Phagocytosis through a Novel Osteopontin Receptor, the {alpha}X{beta}2 Integrin. J. Immunol. 182: 6943-6950 [Abstract] [Full Text]  
  • Karcher, E. L., Bayles, D. O., Bannantine, J. P., Beitz, D. C., Stabel, J. R. (2008). Osteopontin: A Novel Cytokine Involved in the Regulation of Mycobacterium avium subspecies paratuberculosis Infection in Periparturient Dairy Cattle. J DAIRY SCI 91: 3079-3091 [Abstract] [Full Text]  
  • Scatena, M., Liaw, L., Giachelli, C. M. (2007). Osteopontin: A Multifunctional Molecule Regulating Chronic Inflammation and Vascular Disease. Arterioscler. Thromb. Vasc. Bio. 27: 2302-2309 [Abstract] [Full Text]  
  • O'Riordan, K., Sharlin, D. S., Gross, J., Chang, S., Errabelli, D., Akilov, O. E., Kosaka, S., Nau, G. J., Hasan, T. (2006). Photoinactivation of Mycobacteria In Vitro and in a New Murine Model of Localized Mycobacterium bovis BCG-Induced Granulomatous Infection.. Antimicrob. Agents Chemother. 50: 1828-1834 [Abstract] [Full Text]  
  • Sodek, J., Batista Da Silva, A. P., Zohar, R. (2006). Osteopontin and Mucosal Protection. JDR 85: 404-415 [Abstract] [Full Text]  
  • Maeno, Y., Nakazawa, S., Yamamoto, N., Shinzato, M., Nagashima, S., Tanaka, K., Sasaki, J., Rittling, S. R., Denhardt, D. T., Uede, T., Taniguchi, K. (2006). Osteopontin Participates in Th1-Mediated Host Resistance against Nonlethal Malaria Parasite Plasmodium chabaudi chabaudi Infection in Mice. Infect. Immun. 74: 2423-2427 [Abstract] [Full Text]  
  • Tomioka, H., Sano, C., Sato, K., Ogasawara, K., Akaki, T., Sano, K., Cai, S. S., Shimizu, T. (2005). Combined Effects of ATP on the Therapeutic Efficacy of Antimicrobial Drug Regimens against Mycobacterium avium Complex Infection in Mice and Roles of Cytosolic Phospholipase A2-Dependent Mechanisms in the ATP-Mediated Potentiation of Antimycobacterial Host Resistance. J. Immunol. 175: 6741-6749 [Abstract] [Full Text]  
  • Abel, B., Freigang, S., Bachmann, M. F., Boschert, U., Kopf, M. (2005). Osteopontin Is Not Required for the Development of Th1 Responses and Viral Immunity. J. Immunol. 175: 6006-6013 [Abstract] [Full Text]  
  • Renkl, A. C., Wussler, J., Ahrens, T., Thoma, K., Kon, S., Uede, T., Martin, S. F., Simon, J. C., Weiss, J. M. (2005). Osteopontin functionally activates dendritic cells and induces their differentiation toward a Th1-polarizing phenotype. Blood 106: 946-955 [Abstract] [Full Text]  
  • Sato, I., Yamamoto, N., Yamazaki, H., Hashimoto, S., Hino, M., Sakai, F., Fujie, A. (2005). Prevention of the Cryptic Epitope SLAYGLR within Osteopontin Does Not Influence Susceptibility to Candida albicans Infection. Antimicrob. Agents Chemother. 49: 3053-3055 [Abstract] [Full Text]  
  • Stier, S., Ko, Y., Forkert, R., Lutz, C., Neuhaus, T., Grunewald, E., Cheng, T., Dombkowski, D., Calvi, L. M., Rittling, S. R., Scadden, D. T. (2005). Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size. JEM 201: 1781-1791 [Abstract] [Full Text]  
  • Craig-Mylius, K., Weber, G. F., Coburn, J., Glickstein, L. (2005). Borrelia burgdorferi, an extracellular pathogen, circumvents osteopontin in inducing an inflammatory cytokine response. J. Leukoc. Biol. 77: 710-718 [Abstract] [Full Text]  
  • Kawamura, K., Iyonaga, K., Ichiyasu, H., Nagano, J., Suga, M., Sasaki, Y. (2005). Differentiation, Maturation, and Survival of Dendritic Cells by Osteopontin Regulation. CVI 12: 206-212 [Abstract] [Full Text]  
  • Schellings, M. W.M., Pinto, Y. M., Heymans, S. (2004). Matricellular proteins in the heart: possible role during stress and remodeling. Cardiovasc Res 64: 24-31 [Abstract] [Full Text]  
  • Saito, K., Ohara, N., Hotokezaka, H., Fukumoto, S., Yuasa, K., Naito, M., Fujiwara, T., Nakayama, K. (2004). Infection-induced Up-regulation of the Costimulatory Molecule 4-1BB in Osteoblastic Cells and Its Inhibitory Effect on M-CSF/RANKL-induced in Vitro Osteoclastogenesis. J. Biol. Chem. 279: 13555-13563 [Abstract] [Full Text]  
  • Tanaka, K., Morimoto, J., Kon, S., Kimura, C., Inobe, M., Diao, H., Hirschfeld, G., Weiss, J. M., Uede, T. (2004). Effect of Osteopontin Alleles on {beta}-Glucan-Induced Granuloma Formation in the Mouse Liver. Am. J. Pathol. 164: 567-575 [Abstract] [Full Text]  
  • Heldwein, K. A., Liang, M. D., Andresen, T. K., Thomas, K. E., Marty, A. M., Cuesta, N., Vogel, S. N., Fenton, M. J. (2003). TLR2 and TLR4 serve distinct roles in the host immune response against Mycobacterium bovis BCG. J. Leukoc. Biol. 74: 277-286 [Abstract] [Full Text]  
  • Hirata, A., Masuda, S., Tamura, T., Kai, K., Ojima, K., Fukase, A., Motoyoshi, K., Kamakura, K., Miyagoe-Suzuki, Y., Takeda, S.'i. (2003). Expression Profiling of Cytokines and Related Genes in Regenerating Skeletal Muscle after Cardiotoxin Injection: A Role for Osteopontin. Am. J. Pathol. 163: 203-215 [Abstract] [Full Text]  
  • Koguchi, Y., Kawakami, K., Uezu, K., Fukushima, K., Kon, S., Maeda, M., Nakamoto, A., Owan, I., Kuba, M., Kudeken, N., Azuma, M., Yara, S., Shinzato, T., Higa, F., Tateyama, M., Kadota, J.-I., Mukae, H., Kohno, S., Uede, T., Saito, A. (2003). High Plasma Osteopontin Level and Its Relationship with Interleukin-12-mediated Type 1 T Helper Cell Response in Tuberculosis. Am. J. Respir. Crit. Care Med. 167: 1355-1359 [Abstract] [Full Text]  
  • Waters, W. R., Rahner, T. E., Palmer, M. V., Cheng, D., Nonnecke, B. J., Whipple, D. L. (2003). Expression of L-Selectin (CD62L), CD44, and CD25 on Activated Bovine T Cells. Infect. Immun. 71: 317-326 [Abstract] [Full Text]  
  • Koguchi, Y., Kawakami, K., Kon, S., Segawa, T., Maeda, M., Uede, T., Saito, A. (2002). Penicillium marneffei Causes Osteopontin-Mediated Production of Interleukin-12 by Peripheral Blood Mononuclear Cells. Infect. Immun. 70: 1042-1048 [Abstract] [Full Text]  
  • Potter, M. R., Rittling, S. R., Denhardt, D. T., Roper, R. J., Weis, J. H., Teuscher, C., Weis, J. J. (2002). Role of Osteopontin in Murine Lyme Arthritis and Host Defense against Borrelia burgdorferi. Infect. Immun. 70: 1372-1381 [Abstract] [Full Text]  
  • Mazzali, M., Kipari, T., Ophascharoensuk, V., Wesson, J.A., Johnson, R., Hughes, J. (2002). Osteopontin--a molecule for all seasons. QJM 95: 3-13 [Full Text]  
  • O'REGAN, A. W., HAYDEN, J. M., BODY, S., LIAW, L., MULLIGAN, N., GOETSCHKES, M., BERMAN, J. S. (2001). Abnormal Pulmonary Granuloma Formation in Osteopontin-deficient Mice. Am. J. Respir. Crit. Care Med. 164: 2243-2247 [Abstract] [Full Text]  
  • Weiss, J.M., Renkl, A.C., Maier, C.S., Kimmig, M., Liaw, L., Ahrens, T., Kon, S., Maeda, M., Hotta, H., Uede, T., Simon, J.C. (2001). Osteopontin Is Involved in the Initiation of Cutaneous Contact Hypersensitivity by Inducing Langerhans and Dendritic Cell Migration to Lymph Nodes. JEM 194: 1219-1230 [Abstract] [Full Text]  
  • O’Regan, A. W., Hayden, J. M, Berman, J. S. (2000). Osteopontin augments CD3-mediated interferon-{gamma} and CD40 ligand expression by T cells, which results in IL-12 production from peripheral blood mononuclear cells. J. Leukoc. Biol. 68: 495-502 [Abstract] [Full Text]  
  • Nau, G. J., Chupp, G. L., Emile, J.-F., Jouanguy, E., Berman, J. S., Casanova, J.-L., Young, R. A. (2000). Osteopontin Expression Correlates with Clinical Outcome in Patients with Mycobacterial Infection. Am. J. Pathol. 157: 37-42 [Abstract] [Full Text]  
  • Bayless, K. J., Davis, G. E. (2001). Identification of Dual alpha 4beta 1 Integrin Binding Sites within a 38 Amino Acid Domain in the N-terminal Thrombin Fragment of Human Osteopontin. J. Biol. Chem. 276: 13483-13489 [Abstract] [Full Text]  
  • Agnihotri, R., Crawford, H. C., Haro, H., Matrisian, L. M., Havrda, M. C., Liaw, L. (2001). Osteopontin, a Novel Substrate for Matrix Metalloproteinase-3 (Stromelysin-1) and Matrix Metalloproteinase-7 (Matrilysin). J. Biol. Chem. 276: 28261-28267 [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»