期刊
MUCOSAL IMMUNOLOGY
卷 11, 期 3, 页码 968-978出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/mi.2017.80
关键词
-
类别
资金
- National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIH/NIAID) [AI073856, AI093570]
- National Institute on Aging at the National Institute of Health [AG051428]
- Ohio State University (OSU) College of Medicine Systems in Integrative Biology Training Program-NIH/NIGMS [T32-GM068412]
- NIH/NIAID [AI093570-S1]
- CTSA from the National Center for Advancing Translational Sciences [UL1TR001070]
- Comparative Pathology and Mouse Phenotyping Shared Resource in the Department of Veterinary Biosciences [P30 CA016058]
Current tuberculosis (TB) treatments include chemotherapy and preventative vaccination with Mycobacterium bovis Bacillus Calmette-Guerin (BCG). In humans, however, BCG vaccination fails to fully protect against pulmonary TB. Few studies have considered the impact of the human lung mucosa (alveolar lining fluid (ALF)), which modifies the Mycobacterium tuberculosis (M.tb) cell wall, revealing alternate antigenic epitopes on the bacterium surface that alter its pathogenicity. We hypothesized that ALF-induced modification of BCG would induce better protection against aerosol infection with M.tb. Here we vaccinated mice with ALF-exposed BCG, mimicking the mycobacterial cell surface properties that would be present in the lung during M.tb infection. ALF-exposed BCG-vaccinated mice were more effective at reducing M. tb bacterial burden in the lung and spleen, and had reduced lung inflammation at late stages of M. tb infection. Improved BCG efficacy was associated with increased numbers of memory CD8(+) Tcells, and CD8(+) T cells with the potential to produce interferon-gamma in the lung in response to M.tb challenge. Depletion studies confirmed an essential role for CD8(+) Tcells in controlling M.tb bacterial burden. We conclude that ALF modifications to the M. tb cell wall in vivo are relevant in the context of vaccine design.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据