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Control of Mycobacterial Infections in Mice Expressing Human Tumor Necrosis Factor (TNF) but Not Mouse TNFстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 19 сентября 2015 г.
- Авторы: Olleros ML, Chavez-Galan L., Segueni N., Bourigault ML, Vesin D., Kruglov AA, Drutskaya MS, Bisig R., Ehlers S., Aly S., Walter K., Kuprash DV, Chouchkova M., Kozlov SV, Erard F., Ryffel B., Quesniaux VF, Nedospasov SA, Garcia I.
- Журнал: Infection and Immunity
- Том: 83
- Номер: 9
- Год издания: 2015
- Издательство: American Society for Microbiology
- Местоположение издательства: United States
- Первая страница: 3612
- Последняя страница: 3623
- DOI: 10.1128/IAI.00743-15
- Аннотация: Tumor necrosis factor (TNF) is an important cytokine for host defense against pathogens but is also associated with the development of human immunopathologies. TNF blockade effectively ameliorates many chronic inflammatory conditions but compromises host immunity to tuberculosis. The search for novel, more specific human TNF blockers requires the development of a reliable animal model. We used a novel mouse model with complete replacement of the mouse TNF gene by its human ortholog (human TNF [huTNF] knock-in [KI] mice) to determine resistance to Mycobacterium bovis BCG and M. tuberculosis infections and to investigate whether TNF inhibitors in clinical use reduce host immunity. Our results show that macrophages from huTNF KI mice responded to BCG and lipopolysaccharide similarly to wild-type macrophages by NF-κB activation and cytokine production. While TNF-deficient mice rapidly succumbed to mycobacterial infection, huTNF KI mice survived, controlling the bacterial burden and activating bactericidal mechanisms. Administration of TNF-neutralizing biologics disrupted the control of mycobacterial infection in huTNF KI mice, leading to an increased bacterial burden and hyperinflammation. Thus, our findings demonstrate that human TNF can functionally replace murine TNF in vivo, providing mycobacterial resistance that could be compromised by TNF neutralization. This new animal model will be helpful for the testing of specific biologics neutralizing human TNF.
- Добавил в систему: Несмиянов Павел Павлович