IAI FigSearch
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
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 Olszewski, M. A.
Right arrow Articles by Toews, G. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Olszewski, M. A.
Right arrow Articles by Toews, G. B.

 Previous Article  |  Next Article 

Infection and Immunity, October 2001, p. 6256-6263, Vol. 69, No. 10
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.10.6256-6263.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Regulatory Effects of Macrophage Inflammatory Protein 1alpha /CCL3 on the Development of Immunity to Cryptococcus neoformans Depend on Expression of Early Inflammatory Cytokines

Michal A. Olszewski,1,2 Gary B. Huffnagle,2,* Timothy R. Traynor,2 Roderick A. McDonald,2 Donald N. Cook,3 and Galen B. Toews1,2

VA Medical Center Ann Arbor1 and Division of Pulmonary and Critical Care Medicine, The University of Michigan Medical School,2 Ann Arbor, Michigan, and Division of Pulmonary Medicine, Duke University, Durham, North Carolina3

Received 23 April 2001/Returned for modification 31 May 2001/Accepted 28 June 2001

Macrophage inflammatory protein 1alpha (MIP-1alpha )/CCL3 prevents the development of eosinophilic pneumonia (EP) driven by a nonprotective T2-type immunity during infection with a highly virulent strain of Cryptococcus neoformans. The present study evaluated the interaction of MIP-1alpha with other innate immune system cytokines by comparing the immune responses that followed pulmonary infections with high- (C. neoformans 145A) and low (C. neoformans 52D)-virulence strains. In contrast to what was found for C. neoformans 145A infection, lack of MIP-1alpha in C. neoformans 52D infection did not cause the development of EP. C. neoformans 52D induced tumor necrosis factor alpha (TNF-alpha ), gamma interferon (IFN-gamma ), and MCP-1 in the lungs of infected wild-type (WT) and MIP-1alpha knockout (KO) mice by day 7 postinfection. Both WT and MIP-1alpha KO mice subsequently cleared this infection. Thus, the robust expression of early inflammatory cytokines in C. neoformans 52D-infected mice promoted the development of protective immunity even in the absence of MIP-1alpha . Alternatively, C. neoformans 145A-infected WT and MIP-1alpha KO mice had diminished TNF-alpha , IFN-gamma , and macrophage chemoattractant protein 1 (MCP-1) responses, indicating that virulent C. neoformans 145A evaded early innate host defenses. However C. neoformans 145A-infected WT mice had an early induction of MIP-1alpha and subsequently did not develop EP. In contrast, C. neoformans 145A-infected MIP-1alpha KO mice developed EP and had increased C. neoformans dissemination into the brain by day 35. We conclude that, in the absence of other innate immune response effector molecules, MIP-1alpha is crucial to prevent the development of EP and to control C. neoformans dissemination to the brain.

* Corresponding author. Mailing address: Pulmonary and Critical Care Medicine, 6301 MSRB III, University of Michigan Medical Center, Ann Arbor, MI 48109-0642. Phone: (734) 936-9369. Fax: (734) 764-4556. E-mail: ghuff{at}umich.edu.

Infection and Immunity, October 2001, p. 6256-6263, Vol. 69, No. 10
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.10.6256-6263.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2001 by the American Society for Microbiology. All rights reserved.