Regulatory Effects of Macrophage Inflammatory Protein 1α/CCL3 on the Development of Immunity toCryptococcus neoformansDepend on Expression of Early Inflammatory Cytokines
Open Access
- 1 October 2001
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 69 (10), 6256-6263
- https://doi.org/10.1128/iai.69.10.6256-6263.2001
Abstract
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.Keywords
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