Article

Antimicrobial effects of interferon-inducible CXC chemokines against Bacillus anthracis spores and bacilli.

Department of Medicine, Division of Infectious Diseases, University of Virginia Health Sciences System, Charlottesville, VA 22908, USA.
Infection and immunity (Impact Factor: 4.16). 02/2009; 77(4):1664-78. DOI: 10.1128/IAI.01208-08
Source: PubMed

ABSTRACT Based on previous studies showing that host chemokines exert antimicrobial activities against bacteria, we sought to determine whether the interferon-inducible Glu-Leu-Arg-negative CXC chemokines CXCL9, CXCL10, and CXCL11 exhibit antimicrobial activities against Bacillus anthracis. In vitro analysis demonstrated that all three CXC chemokines exerted direct antimicrobial effects against B. anthracis spores and bacilli including marked reductions in spore and bacillus viability as determined using a fluorometric assay of bacterial viability and CFU determinations. Electron microscopy studies revealed that CXCL10-treated spores failed to undergo germination as judged by an absence of cytological changes in spore structure that occur during the process of germination. Immunogold labeling of CXCL10-treated spores demonstrated that the chemokine was located internal to the exosporium in association primarily with the spore coat and its interface with the cortex. To begin examining the potential biological relevance of chemokine-mediated antimicrobial activity, we used a murine model of inhalational anthrax. Upon spore challenge, the lungs of C57BL/6 mice (resistant to inhalational B. anthracis infection) had significantly higher levels of CXCL9, CXCL10, and CXCL11 than did the lungs of A/J mice (highly susceptible to infection). Increased CXC chemokine levels were associated with significantly reduced levels of spore germination within the lungs as determined by in vivo imaging. Taken together, our data demonstrate a novel antimicrobial role for host chemokines against B. anthracis that provides unique insight into host defense against inhalational anthrax; these data also support the notion for an innovative approach in treating B. anthracis infection as well as infections caused by other spore-forming organisms.

0 Bookmarks
 · 
98 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Herein we describe the capacity of Bacillus anthracis peptidoglycan (BaPGN) to trigger an antimicrobial response in human white blood cells (WBCs). Analysis of freshly isolated human blood cells found that monocytes and neutrophils, but not B and T-cells, were highly responsive to BaPGN and produced a variety of cytokines and chemokines. This BaPGN-induced response was suppressed by anthrax lethal toxin (LT) and edema toxin (ET) with the most pronounced effect on human monocytes, and this corresponded with the higher levels of ANTXR1 in these cells compared to neutrophils. The supernatant from BaPGN-treated cells altered the growth of B. anthracis Sterne and this effect was blocked by LT, but not by ET. A FtsX mutant of B. anthracis known to be resistant to the antimicrobial effects of interferon-inducible ELR-negative CXC-chemokines, was not affected by the BaPGN-induced antimicrobial effects. Collectively, these findings describe a system wherein BaPGN triggers expression of antimicrobial factors in human WBCs and reveal a distinctive role, not shared with ET, in LT's capacity to suppress this response.
    Infection and immunity 07/2013; DOI:10.1128/IAI.00709-13 · 4.16 Impact Factor
  • Source
    Medycyna weterynaryjna 01/2011; 67(10):665-668. · 0.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We previously showed that topical flagellin induces profound mucosal innate protection in the cornea against microbial infection, a response involving multiple genes and cell types. In this study, we used a Candida albicans (CA)-C57BL/6 mouse keratitis model to delineate the contribution of CXCL10 and CXCR3-expressing cells in flagellin-induced protection. Flagellin-pretreatment markedly enhanced CXCL10 expression at 6 hours post CA infection (hpi), but significantly dampened CXCL10 expression at 24 hpi. At the cellular level, CXCL10 was expressed in the epithelia at 6 hpi in flagellin-pretreated corneas, and concentrated at lesion sites 24 hpi. CXCR3-expressing cells were detected in great numbers at 24 hpi, organized within clusters at the lesion sites in CA-infected corneas. CXCL10 or CXCR3 neutralization increased keratitis severity and dampened flagellin-induced protection. CXCR3-positive cells were identified as NK cells, the depletion of which resulted in severe CA keratitis. Contributions from NK T-cells were excluded by finding no change in flagellin-induced protection in Rag1 knockout mice. Recombinant CXCL10 inhibited CA growth in vitro and accelerated fungal clearance and inflammation resolution in vivo. Taken together, our data indicate that epithelium-expressed CXCL10 plays a critical role in fungal clearance and that CXCR3-expressing NK cells contribute to CA eradication in mouse corneas.This article is protected by copyright. All rights reserved
    European Journal of Immunology 09/2014; 44(9). DOI:10.1002/eji.201444490 · 4.52 Impact Factor

Full-text (2 Sources)

Download
16 Downloads
Available from
May 23, 2014