Involvement of endogenously synthesized interleukin (IL)-18 in the protective effects of IL-12 against pulmonary infection withCryptococcus neoformansin mice
| Autor: | Kiyoshi Takeda, Mahboob Hossain Qureshi, Tiantuo Zhang, Shizuo Akira, Masashi Kurimoto, Yoshinobu Koguchi, Satomi Yara, Kazuyoshi Kawakami, Atsushi Saito |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Microbiology (medical)
medicine.medical_treatment Immunology Caspase 1 Microbiology Interferon-gamma Mice Interferon medicine Animals Humans Immunology and Allergy Interferon gamma Lung Cryptococcus neoformans Lung Diseases Fungal biology Reverse Transcriptase Polymerase Chain Reaction Interleukin-18 Interleukin RNA Fungal Cryptococcosis General Medicine biology.organism_classification Interleukin-12 Mice Inbred C57BL Infectious Diseases Cytokine Interleukin 12 Female Tumor necrosis factor alpha Rabbits Bronchoalveolar Lavage Fluid medicine.drug |
| Zdroj: | FEMS Immunology & Medical Microbiology. 27:191-200 |
| ISSN: | 1574-695X 0928-8244 |
| DOI: | 10.1111/j.1574-695x.2000.tb01430.x |
| Popis: | We previously demonstrated that interleukin (IL)-12 protected mice against fatal pulmonary infection with a highly virulent strain of Cryptococcus neoformans, which correlated well with the production of interferon (IFN)-gamma as well as IL-18 in the primary infected site. In the present study, we examined the role of endogenously synthesized IL-18 in IL-12-induced host resistance to this pathogen. There was little or no production of IFN-gamma and IL-18 both at mRNA and protein levels in lungs of mice infected with C. neoformans, while treatment with IL-12 induced a marked production of these cytokines. Caspase-1 mRNA was expressed in infected mice even without IL-12 treatment. Administration of neutralizing anti-IFN-gamma monoclonal antibody (mAb) clearly inhibited production of IFN-gamma and IL-18 induced by IL-12, while control IgG did not show such an effect. However, administration of IFN-gamma did not induce the production of both cytokines in infected mice, although tumor necrosis factor (TNF)-alpha and IFN-gamma-inducible protein (IP)-10 were synthesized by the same treatment. Finally, neutralizing anti-IL-18 antibody (Ab) significantly interfered with the production of IFN-gamma and elimination of the microorganism from the lung induced by IL-12 treatment. Furthermore, both IFN-gamma synthesis and host protection caused by IL-12 were profoundly diminished in IL-18 gene-disrupted mice. Considered collectively, our results indicated that host protection against C. neoformans induced by IL-12 involved endogenously synthesized IL-18 and that the production of IL-18 was mediated at least in part by endogenous IFN-gamma. |
| Databáze: | OpenAIRE |
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