RGD Reference Report - Chemokine receptor CXCR2 mediates bacterial clearance rather than neutrophil recruitment in a murine model of pneumonic plague. - Rat Genome Database

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Chemokine receptor CXCR2 mediates bacterial clearance rather than neutrophil recruitment in a murine model of pneumonic plague.

Authors: Eisele, NA  Lee-Lewis, H  Besch-Williford, C  Brown, CR  Anderson, DM 
Citation: Eisele NA, etal., Am J Pathol. 2011 Mar;178(3):1190-200.
RGD ID: 5134954
Pubmed: PMID:21356370   (View Abstract at PubMed)
PMCID: PMC3070576   (View Article at PubMed Central)
DOI: DOI:10.1016/j.ajpath.2010.11.067   (Journal Full-text)

Pulmonary infection by Yersinia pestis causes pneumonic plague, a necrotic bronchopneumonia that is rapidly lethal and highly contagious. Acute pneumonic plague accompanies the up-regulation of pro-inflammatory cytokines and chemokines, suggesting that the host innate immune response may contribute to the development of disease. To address this possibility, we sought to understand the consequences of neutrophil recruitment during pneumonic plague, and we studied the susceptibility of C3H-HeN mice lacking the CXC chemokine KC or its receptor CXC receptor 2 (CXCR2) to pulmonary Y. pestis infection. We found that without Kc or Cxcr2, disease progression was accelerated both in bacterial growth and development of primary bronchopneumonia. When examined in an antibody clearance model, Cxcr2(-/-) mice were not protected by neutralizing Y. pestis antibodies, yet bacterial growth in the lungs was delayed in a manner associated with a neutrophil-mediated inflammatory response. After this initial delay, however, robust neutrophil recruitment in Cxcr2(-/-) mice correlated with bacterial growth and the development of fulminant pneumonic and septicemic plague. In contrast, attenuated Y. pestis lacking the conserved pigmentation locus could be cleared from the lungs in the absence of Cxcr2 indicating virulence factors within this locus may inhibit CXCR2-independent pathways of bacterial killing. Together, the data suggest CXCR2 uniquely induces host defense mechanisms that are effective against virulent Y. pestis, raising new insight into the activation of neutrophils during infection.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
bronchopneumonia disease_progressionISOCxcr2 (Mus musculus)5134954; 5134954associated with PlagueRGD 
bronchopneumonia disease_progressionIMP 5134954associated with PlagueRGD 
plague  ISOCxcl1 (Mus musculus)5134954; 5134954 RGD 
plague  IMP 5134954 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cxcl1  (C-X-C motif chemokine ligand 1)
Cxcr2  (C-X-C motif chemokine receptor 2)

Genes (Mus musculus)
Cxcl1  (C-X-C motif chemokine ligand 1)
Cxcr2  (C-X-C motif chemokine receptor 2)

Genes (Homo sapiens)
CXCL1  (C-X-C motif chemokine ligand 1)
CXCR2  (C-X-C motif chemokine receptor 2)


Additional Information