title: Chemokine receptor CXCR2 mediates bacterial clearance rather than neutrophil recruitment in a murine model of pneumonic plague.
abstract: 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.
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri 65211, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Eisele
authors.forename: Hanni
authors.initials: H
authors.lastname: Lee-Lewis
authors.forename: Cynthia
authors.initials: C
authors.lastname: Besch-Williford
authors.forename: Charles R
authors.initials: CR
authors.lastname: Brown
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Anderson
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D054360:Chemokine CXCL1 / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018448:Models, Immunological; D009154:Mutation / Q000235:genetics; D020556:Neutrophil Infiltration / Q000276:immunology*; D010930:Plague / Q000276:immunology* / Q000382:microbiology* / Q000517:prevention & control; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology; D023063:Receptors, Interleukin-8B / Q000378:metabolism*; D015398:Signal Transduction; D015010:Yersinia pestis / Q000254:growth & development / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; C043908:LcrV protein, Yersinia; D052899:Pore Forming Cytotoxic Proteins; D023063:Receptors, Interleukin-8B