Human Lung Innate Immune Response to Bacillus anthracis Spore Infection

Bacillus anthracis, the causative agent of inhalational anthrax, enters a host through the pulmonary system before dissemination. We have previously shown that human alveolar macrophages participate in the initial innate immune response to B. anthracis spores through cell signal-mediated cytokine re...

Full description

Saved in:
Bibliographic Details
Published in:Infection and Immunity 2007-08, Vol.75 (8), p.3729-3738
Main Authors: Chakrabarty, Kaushik, Wu, Wenxin, Booth, J. Leland, Duggan, Elizabeth S, Nagle, Nancy N, Coggeshall, K. Mark, Metcalf, Jordan P
Format: Article
Language:English
Subjects:
Anthracenes - pharmacology
Anthrax - immunology
Bacillus anthracis
Bacillus anthracis - immunology
Bacteriology
Biological and medical sciences
Butadienes - pharmacology
Chemokines - biosynthesis
Chemokines - immunology
Cytokines - biosynthesis
Cytokines - immunology
Enzyme Inhibitors - pharmacology
Enzyme-Linked Immunosorbent Assay
Epithelial Cells - immunology
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Host Response and Inflammation
Humans
Imidazoles - pharmacology
Immunity, Innate
Immunohistochemistry
In Vitro Techniques
Lung - cytology
Lung - immunology
Lung - microbiology
Macrophages, Alveolar - immunology
MAP Kinase Signaling System - drug effects
MAP Kinase Signaling System - immunology
Microbiology
Microscopy, Fluorescence
Miscellaneous
Nitriles - pharmacology
Pulmonary Alveoli - pathology
Pyridines - pharmacology
RNA, Messenger - analysis
Spores, Bacterial - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Bacillus anthracis, the causative agent of inhalational anthrax, enters a host through the pulmonary system before dissemination. We have previously shown that human alveolar macrophages participate in the initial innate immune response to B. anthracis spores through cell signal-mediated cytokine release. We proposed that the lung epithelia also participate in the innate immune response to this pathogen, and we have developed a human lung slice model to study this process. Exposure of our model to B. anthracis (Sterne) spores rapidly activated the mitogen-activated protein kinase signaling pathways ERK, p38, and JNK. In addition, an RNase protection assay showed induction of mRNA of several cytokines and chemokines. This finding was reflected at the translational level by protein peak increases of 3-, 25-, 9-, 34-, and 5-fold for interleukin-6 (IL-6), tumor necrosis factor alpha, IL-8, macrophage inflammatory protein 1α/β, and monocyte chemoattractant protein 1, respectively, as determined by an enzyme-linked immunosorbent assay. Inhibition of individual pathways by UO126, SP600125, and SB0203580 decreased induction of chemokines and cytokines by spores, but this depended on the pathways inhibited and the cytokines and chemokines induced. Combining all three inhibitors reduced induction of all cytokines and chemokines tested to background levels. An immunohistochemistry analysis of IL-6 and IL-8 revealed that alveolar epithelial cells and macrophages and a few interstitial cells are the source of the cytokines and chemokines. Taken together, these data showed the activation of the pulmonary epithelium in response to B. anthracis spore exposure. Thus, the lung epithelia actively participate in the innate immune response to B. anthracis infection through cell signal-mediated elaboration of cytokines and chemokines.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.00046-07