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 Brieland, J. K.
Right arrow Articles by O'Garra, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brieland, J. K.
Right arrow Articles by O'Garra, A.

 Previous Article  |  Next Article 

Infection and Immunity, March 2001, p. 1554-1560, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1554-1560.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Cytokine Networking in Lungs of Immunocompetent Mice in Response to Inhaled Aspergillus fumigatus

Joan K. Brieland,1,* Craig Jackson,1 Fred Menzel,1 David Loebenberg,1 Anthony Cacciapuoti,1 Judy Halpern,1 Stephen Hurst,2 Tony Muchamuel,2 Reno Debets,2 Rob Kastelein,2 Tatyana Churakova,2 John Abrams,2 Roberta Hare,1 and Anne O'Garra2

Department of Chemotherapy, Schering Plough Research Institute, Kenilworth, New Jersey,1 and DNAX Research Institute, Palo Alto, California2

Received 30 October 2000/Returned for modification 8 December 2000/Accepted 15 December 2000

Cytokine networking in the lung in response to inhaled Aspergillus fumigatus was assessed using a murine model of primary pulmonary aspergillosis in immunocompetent Crl:CF-1 mice. Inhalation of virulent A. fumigatus (6 × 106 CFU) resulted in the induction of interleukin 18 (IL-18), tumor necrosis factor alpha (TNF-alpha ), IL-12, and gamma interferon (IFN-gamma ) protein in bronchoalveolar lavage fluid and/or lung tissue. Induction of immunoreactive IL-18 preceded induction of TNF-alpha protein, which preceded induction of immunoreactive IL-12 and IFN-gamma . Real-time reverse transcriptase (RT) PCR analysis of infected lung tissue demonstrated that induction of IL-18 protein also preceded induction of pulmonary TNF-alpha , IL-12, and IFN-gamma mRNAs. Mice were subsequently treated with cytokine-specific neutralizing monoclonal antibodies (MAbs) to the IL-18 receptor (anti-IL-18R MAb), TNF-alpha (anti-TNF-alpha MAb), IL-12 (anti-IL-12 MAb), and/or IFN-gamma (anti-IFN-gamma MAb), and effects on intrapulmonary cytokine activity and growth of A. fumigatus were assessed in infected lung homogenates. Simultaneous neutralization of IL-12 and IL-18 resulted in decreased levels of immunoreactive TNF-alpha , while neutralization of IL-18, TNF-alpha , or IL-12 alone or of IL-18 and IL-12 together resulted in decreased levels of immunoreactive IFN-gamma . Simultaneous neutralization of IL-12 and IL-18 or neutralization of TNF-alpha alone or in combination with IL-12, IL-18, or IFN-gamma also resulted in a significant increase in A. fumigatus CFU in lung tissue. Taken together, these results demonstrate that endogenous IL-18, IL-12, and TNF-alpha , through their modulatory effects on both intrapulmonary cytokine activity and growth of A. fumigatus, play key roles in host defense against primary pulmonary aspergillosis.

* Corresponding author. Mailing address: Schering Plough Research Institute, 2015 Galloping Hill Rd., K15-B432 4800, Kenilworth, NJ 07033. Phone: (908) 740-3147. Fax: (908) 740-3918. E-mail: joan.brieland{at}spcorp.com.

Infection and Immunity, March 2001, p. 1554-1560, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1554-1560.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Park, S. J., Mehrad, B. (2009). Innate Immunity to Aspergillus Species. Clin. Microbiol. Rev. 22: 535-551 [Abstract] [Full Text]  
  • Thrasher, J. D, Crawley, S. (2009). The biocontaminants and complexity of damp indoor spaces: more than what meets the eyes. Toxicol Ind Health 25: 583-615 [Abstract]  
  • Dagenais, T. R. T., Keller, N. P. (2009). Pathogenesis of Aspergillus fumigatus in Invasive Aspergillosis. Clin. Microbiol. Rev. 22: 447-465 [Abstract] [Full Text]  
  • Rivera, A., Collins, N., Stephan, M. T., Lipuma, L., Leiner, I., Pamer, E. G. (2009). Aberrant Tissue Localization of Fungus-Specific CD4+ T Cells in IL-10-Deficient Mice. J. Immunol. 183: 631-641 [Abstract] [Full Text]  
  • Park, S. J., Hughes, M. A., Burdick, M., Strieter, R. M., Mehrad, B. (2009). Early NK Cell-Derived IFN-{gamma} Is Essential to Host Defense in Neutropenic Invasive Aspergillosis. J. Immunol. 182: 4306-4312 [Abstract] [Full Text]  
  • Tsiodras, S., Samonis, G., Boumpas, D. T., Kontoyiannis, D. P. (2008). Fungal Infections Complicating Tumor Necrosis Factor {alpha} Blockade Therapy. Mayo Clin Proc. 83: 181-194 [Abstract] [Full Text]  
  • Simitsopoulou, M., Roilides, E., Likartsis, C., Ioannidis, J., Orfanou, A., Paliogianni, F., Walsh, T. J. (2007). Expression of Immunomodulatory Genes in Human Monocytes Induced by Voriconazole in the Presence of Aspergillus fumigatus. Antimicrob. Agents Chemother. 51: 1048-1054 [Abstract] [Full Text]  
  • Lean, I-S., Lacroix-Lamande, S., Laurent, F., McDonald, V. (2006). Role of Tumor Necrosis Factor Alpha in Development of Immunity against Cryptosporidium parvum Infection. Infect. Immun. 74: 4379-4382 [Abstract] [Full Text]  
  • Herring, A. C., Falkowski, N. R., Chen, G.-H., McDonald, R. A., Toews, G. B., Huffnagle, G. B. (2005). Transient Neutralization of Tumor Necrosis Factor Alpha Can Produce a Chronic Fungal Infection in an Immunocompetent Host: Potential Role of Immature Dendritic Cells. Infect. Immun. 73: 39-49 [Abstract] [Full Text]  
  • Stephens-Romero, S. D., Mednick, A. J., Feldmesser, M. (2005). The Pathogenesis of Fatal Outcome in Murine Pulmonary Aspergillosis Depends on the Neutrophil Depletion Strategy. Infect. Immun. 73: 114-125 [Abstract] [Full Text]  
  • Balloy, V., Huerre, M., Latge, J.-P., Chignard, M. (2005). Differences in Patterns of Infection and Inflammation for Corticosteroid Treatment and Chemotherapy in Experimental Invasive Pulmonary Aspergillosis. Infect. Immun. 73: 494-503 [Abstract] [Full Text]  
  • Halpern, M. D., Holubec, H., Dominguez, J. A., Meza, Y. G., Williams, C. S., Ruth, M. C., McCuskey, R. S., Dvorak, B. (2003). Hepatic inflammatory mediators contribute to intestinal damage in necrotizing enterocolitis. Am. J. Physiol. Gastrointest. Liver Physiol. 284: G695-G702 [Abstract] [Full Text]  
  • Mehrad, B., Wiekowski, M., Morrison, B. E., Chen, S.-C., Coronel, E. C., Manfra, D. J., Lira, S. A. (2002). Transient Lung-Specific Expression of the Chemokine KC Improves Outcome in Invasive Aspergillosis. Am. J. Respir. Crit. Care Med. 166: 1263-1268 [Abstract] [Full Text]  
  • Reddy, P., Teshima, T., Hildebrandt, G., Duffner, U., Maeda, Y., Cooke, K. R., Ferrara, J. L. M. (2002). Interleukin 18 preserves a perforin-dependent graft-versus-leukemia effect after allogeneic bone marrow transplantation. Blood 100: 3429-3431 [Abstract] [Full Text]  
  • Mambula, S. S., Sau, K., Henneke, P., Golenbock, D. T., Levitz, S. M. (2002). Toll-like Receptor (TLR) Signaling in Response to Aspergillus fumigatus. J. Biol. Chem. 277: 39320-39326 [Abstract] [Full Text]  
  • Foxman, E. F., Zhang, M., Hurst, S. D., Muchamuel, T., Shen, D., Wawrousek, E. F., Chan, C.-C., Gery, I. (2002). Inflammatory Mediators in Uveitis: Differential Induction of Cytokines and Chemokines in Th1- Versus Th2-Mediated Ocular Inflammation. J. Immunol. 168: 2483-2492 [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»