Inhalation of Francisella novicida ΔmglA causes replicative infection that elicits innate and adaptive responses but is not protective against invasive pneumonic tularemia

被引:19
作者
West, T. Eoin [1 ]
Pelletier, Mark R. [1 ]
Majure, Melanie C. [1 ]
Lembo, Annalisa [1 ]
Hajjar, Adeline M. [2 ]
Skerrett, Shawn J. [1 ]
机构
[1] Univ Washington, Harborview Med Ctr, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98104 USA
[2] Univ Washington, Dept Immunol, Seattle, WA 98195 USA
关键词
Francisella tularensis; tularemia; pneumonia; immunology;
D O I
10.1016/j.micinf.2008.04.008
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:773 / 780
页数:8
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