Differential Effects of Total and Partial Neutralization of Tumor Necrosis Factor on Cell-Mediated Immunity to Mycobacterium bovis BCG Infection
| Autor: | Irene Garcia, Reto Guler, Maria L. Olleros, Dominique Vesin, Roumen Parapanov |
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| Rok vydání: | 2005 |
| Předmět: |
Genetically modified mouse
Mycobacterium bovis/ immunology Cellular immunity medicine.medical_treatment Immunology Nitric Oxide Synthase Type II Mice Transgenic ddc:616.07 Biology Microbiology Interferon-gamma Mice Immune system medicine Animals Tuberculosis Macrophage Interferon gamma Receptors Tumor Necrosis Factor Type I/blood Tumor Necrosis Factor-alpha/antagonists & inhibitors/ physiology Host Response and Inflammation Mice Inbred BALB C Mycobacterium bovis Tumor Necrosis Factor-alpha Nitric Oxide Synthase/metabolism Tuberculosis/ immunology Macrophage Activation biology.organism_classification Mice Inbred C57BL Infectious Diseases Cytokine Receptors Tumor Necrosis Factor Type I Parasitology Tumor necrosis factor alpha Nitric Oxide Synthase Interferon-gamma/blood medicine.drug |
| Zdroj: | Infection and Immunity, Vol. 73, No 6 (2005) pp. 3668-3676 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | The effects of total and partial inhibition of tumor necrosis factor (TNF) on sensitivity to Mycobacterium bovis BCG infection were investigated by using transgenic mice in which hepatocytes produced different amounts of human soluble TNF receptor 1 (sTNFR1) fused to the Fc fragment of human immunoglobulin G3 that could be detected in the serum. Transgenic mice expressing high serum levels of sTNFR1, neutralizing all circulating TNF, failed to develop differentiated granulomas and bactericidal mechanisms, and they succumbed to BCG infection. sTNFR1 transgenic mice did not activate BCG-induced Th1-type cytokines early in infection, but uncontrolled cytokine release was found late in infection. In this work we also evaluated the effect of partial inhibition of TNF on resistance to BCG infection. Transgenic mice expressing low levels of sTNFR1 were protected against BCG infection, and they developed increased bactericidal mechanisms, such as enhanced inducible nitric oxide synthase activity, increased macrophage activation, and showed higher numbers of liver granulomas early in infection compared to their negative littermates. Our data suggest that while total inhibition of TNF prevented BCG-induced cell-mediated immune responses, partial inhibition of TNF could contribute to macrophage activation, induction of bactericidal mechanisms, and granuloma formation in the early phase of BCG infection. |
| Databáze: | OpenAIRE |
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