Human lung innate immune response to Bacillus anthracis spore infection.

Human lung innate immune response to Bacillus anthracis spore infection. Research Abstract Details 

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Human lung innate immune response to Bacillus anthracis spore infection. Abstract Text:

Kaushik Chakrabarty,Wenxin Wu,J Leland Booth,Elizabeth S Duggan,Nancy N Nagle,K Mark Coggeshall,Jordan P Metcalf,

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 1alpha/beta, 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.

Human lung innate immune response to Bacillus anthracis spore infection. Publishing Authors By Initials

K Chakrabarty,W Wu,JL Booth,ES Duggan,NN Nagle,KM Coggeshall,JP Metcalf,

For similar cells: spores: spores, bacterial research abstracts see: cells: spores: spores, bacterial research

PUBMED ID PMID:

MEDLINE DATE:

Human lung innate immune response to Bacillus anthracis spore infection. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Infection and immunity

VOLUME: 75

Page Numbers: 3729-38

Journal Abbreviation: Infect. Immun.

ISSN: 0019-9567

DAY: 21

MONTH: 05

YEAR: 2007

Human lung innate immune response to Bacillus anthracis spore infection. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 246127

Human lung innate immune response to Bacillus anthracis spore infection. Keywords Mesh Terms:

KEYWORDS: Spores, Bacterial

MESH TERMS: immunology

Chemical & Substance for Abstract: Human lung innate immune response to Bacillus anthracis spore infection. Information

Substance Name: anthra(1,9-cd)pyrazol-6(2H)-one

Registry Number: 0

Grant and Affiliation Information for Human lung innate immune response to Bacillus anthracis spore infection.

AFFILIATION: University of Oklahoma Health Sciences Center, 800 N. Research Parkway, Oklahoma City, OK 73104, USA.

Country: United States

AGENCY: United States NIAID

GRANT: U19 AI 62629

ACRONYM: AI

MEDLINETA: Infect Immun

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