RGD Reference Report - Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection. - Rat Genome Database

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Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection.

Authors: Crawford, MA  Burdick, MD  Glomski, IJ  Boyer, AE  Barr, JR  Mehrad, B  Strieter, RM  Hughes, MA 
Citation: Crawford MA, etal., PLoS Pathog. 2010 Nov 18;6(11):e1001199.
RGD ID: 5135283
Pubmed: PMID:21124994   (View Abstract at PubMed)
PMCID: PMC2987825   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.ppat.1001199   (Journal Full-text)

Chemokines have been found to exert direct, defensin-like antimicrobial activity in vitro, suggesting that, in addition to orchestrating cellular accumulation and activation, chemokines may contribute directly to the innate host response against infection. No observations have been made, however, demonstrating direct chemokine-mediated promotion of host defense in vivo. Here, we show that the murine interferon-inducible CXC chemokines CXCL9, CXCL10, and CXCL11 each exert direct antimicrobial effects in vitro against Bacillus anthracis Sterne strain spores and bacilli including disruptions in spore germination and marked reductions in spore and bacilli viability as assessed using CFU determination and a fluorometric assay of metabolic activity. Similar chemokine-mediated antimicrobial activity was also observed against fully virulent Ames strain spores and encapsulated bacilli. Moreover, antibody-mediated neutralization of these CXC chemokines in vivo was found to significantly increase host susceptibility to pulmonary B. anthracis infection in a murine model of inhalational anthrax with disease progression characterized by systemic bacterial dissemination, toxemia, and host death. Neutralization of the shared chemokine receptor CXCR3, responsible for mediating cellular recruitment in response to CXCL9, CXCL10, and CXCL11, was not found to increase host susceptibility to inhalational anthrax. Taken together, our data demonstrate a novel, receptor-independent antimicrobial role for the interferon-inducible CXC chemokines in pulmonary innate immunity in vivo. These data also support an immunomodulatory approach for effectively treating and/or preventing pulmonary B. anthracis infection, as well as infections caused by pathogenic and potentially, multi-drug resistant bacteria including other spore-forming organisms.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CXCL10Humaninhalation anthrax disease_progressionISOCxcl10 (Mus musculus) RGD 
CXCL11Humaninhalation anthrax disease_progressionISOCxcl11 (Mus musculus) RGD 
CXCL9Humaninhalation anthrax disease_progressionISOCxcl9 (Mus musculus) RGD 
Cxcl10Ratinhalation anthrax disease_progressionISOCxcl10 (Mus musculus) RGD 
Cxcl10Mouseinhalation anthrax disease_progressionIMP  RGD 
Cxcl11Ratinhalation anthrax disease_progressionISOCxcl11 (Mus musculus) RGD 
Cxcl11Mouseinhalation anthrax disease_progressionIMP  RGD 
Cxcl9Ratinhalation anthrax disease_progressionISOCxcl9 (Mus musculus) RGD 
Cxcl9Mouseinhalation anthrax disease_progressionIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cxcl10  (C-X-C motif chemokine ligand 10)
Cxcl11  (C-X-C motif chemokine ligand 11)
Cxcl9  (C-X-C motif chemokine ligand 9)

Genes (Mus musculus)
Cxcl10  (C-X-C motif chemokine ligand 10)
Cxcl11  (chemokine (C-X-C motif) ligand 11)
Cxcl9  (C-X-C motif chemokine ligand 9)

Genes (Homo sapiens)
CXCL10  (C-X-C motif chemokine ligand 10)
CXCL11  (C-X-C motif chemokine ligand 11)
CXCL9  (C-X-C motif chemokine ligand 9)


Additional Information