期刊
MICROBES AND INFECTION
卷 10, 期 7, 页码 773-780出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.micinf.2008.04.008
关键词
Francisella tularensis; tularemia; pneumonia; immunology
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL007287] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U54AI057141] Funding Source: NIH RePORTER
- NHLBI NIH HHS [T32 HL007287-30, T32HL07287, T32 HL007287] Funding Source: Medline
- NIAID NIH HHS [U54 AI057141, U54AI057141, U54 AI057141-05] Funding Source: Medline
Francisella tularensis causes the zoonosis tularemia in humans, and inhaled F. tularensis ssp. novicida induces lethal murine tularemia. Transcription of virulence factors in F. novicida is regulated by macrophage growth locus A (mglA), a global regulator required for bacterial replication in macrophages in vitro. We examined the infectivity and immunogenicity of attenuated F. novicida Delta mglA in the lung in vivo. Aerosolized Delta mglA caused replicative pulmonary infection that peaked at 7 days and was cleared thereafter, without clinical evidence of disease. In contrast, inhalation of wild type F. novicida resulted in more rapid bacterial replication and dissemination leading to death within 96 h. Early containment of Delta mglA infection was partially dependent on myeloid differentiation factor 88 and interferon-gamma but did not require B or T cells. However, lymphocytes were necessary for subsequent bacterial clearance. Infection with Delta mglA elicited specific IgG1-predominant antibodies and variable interferon-gamma recall responses to wild type F. novicida. Inoculation of mice with aerosolized Delta mglA afforded no protection against a subsequent low-dose aerosol challenge with wild type F. novicida. These findings establish that inhalation of F. novicida Delta mglA results in replicative infection that elicits innate and adaptive immune responses but not protective immunity against invasive pneumonic tularemia. (C) 2008 Elsevier Masson SAS. All rights reserved.
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