Regulatory Effects of Macrophage Inflammatory Protein 1α/CCL3 on the Development of Immunity toCryptococcus neoformansDepend on Expression of Early Inflammatory Cytokines
| Autor: | Gary B. Huffnagle, Galen B. Toews, Timothy Traynor, Michal A. Olszewski, Roderick A. McDonald, Donald N. Cook |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Central Nervous System
Immunology Gene Expression CCL3 Microbiology Proinflammatory cytokine Interferon-gamma Mice Immune system Immunity Leukocytes medicine Animals Pulmonary Eosinophilia Chemokine CCL4 Lung Macrophage inflammatory protein Chemokine CCL2 Chemokine CCL3 Mice Knockout Cryptococcus neoformans Innate immune system Virulence biology Tumor Necrosis Factor-alpha Gene Expression Profiling Brain Cryptococcosis Macrophage Inflammatory Proteins biology.organism_classification medicine.disease Mice Inbred C57BL Infectious Diseases Parasitology Fungal and Parasitic Infections |
| Zdroj: | Infection and Immunity. 69:6256-6263 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.69.10.6256-6263.2001 |
| Popis: | Macrophage inflammatory protein 1α (MIP-1α)/CCL3 prevents the development of eosinophilic pneumonia (EP) driven by a nonprotective T2-type immunity during infection with a highly virulent strain ofCryptococcus neoformans. The present study evaluated the interaction of MIP-1α with other innate immune system cytokines by comparing the immune responses that followed pulmonary infections with high- (C. neoformans145A) and low (C. neoformans52D)-virulence strains. In contrast to what was found forC. neoformans145A infection, lack of MIP-1α inC. neoformans52D infection did not cause the development of EP.C. neoformans52D induced tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), and MCP-1 in the lungs of infected wild-type (WT) and MIP-1α knockout (KO) mice by day 7 postinfection. Both WT and MIP-1α KO mice subsequently cleared this infection. Thus, the robust expression of early inflammatory cytokines inC. neoformans52D-infected mice promoted the development of protective immunity even in the absence of MIP-1α. Alternatively,C. neoformans145A-infected WT and MIP-1α KO mice had diminished TNF-α, IFN-γ, and macrophage chemoattractant protein 1 (MCP-1) responses, indicating that virulentC. neoformans145A evaded early innate host defenses. HoweverC. neoformans145A-infected WT mice had an early induction of MIP-1α and subsequently did not develop EP. In contrast,C. neoformans145A-infected MIP-1α KO mice developed EP and had increasedC. neoformansdissemination into the brain by day 35. We conclude that, in the absence of other innate immune response effector molecules, MIP-1α is crucial to prevent the development of EP and to controlC. neoformansdissemination to the brain. |
| Databáze: | OpenAIRE |
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