Gammaherpesvirus-induced lung pathology is altered in the absence of macrophages.
The purpose of this study was to examine the lung pathogenesis of murine gammaherpesvirus (MHV-68) infection in mice that lack CC chemokine receptor CCR2, an important receptor for macrophage recruitment to sites of inflammation. BALB/c and CCR2(-/-) mice were inoculated intranasally (i.n.) with MHV-68 and samples were collected during acute infection (6 dpi) and following viral clearance (12 dpi). Immunohistochemistry was used to determine which cells types responded to MHV-68 infection in the lungs. Lung pathology in infected BALB/c mice was characterized by a mixed inflammatory cell infiltrate, necrosis, and increased alveolar macrophages by 12 dpi. Immunohistochemistry showed intense positive staining for macrophages. CCR2(-/-) mice showed greater inflammation in the lungs at 12 dpi than did BALB/c mice, with more necrosis and diffuse neutrophil infiltrates in the alveoli. Immunohistochemistry demonstrated much less macrophage infiltration in the CCR2(-/-) mice than in the BALB/c mice. These studies show that CCR2 is involved in macrophage recruitment in response to MHV-68 infection and illustrates how impairments in macrophage function affect the normal inflammatory response to this viral infection.
Cadillac
J M
JM
Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Sigler
R E
RE
Weinberg
J B
JB
Lutzke
M L
ML
Rochford
R
R
D000818:Animals; D018142:Gammaherpesvirinae; D006566:Herpesviridae Infections / Q000276:immunology / Q000473:pathology*; D008168:Lung / Q000473:pathology* / Q000821:virology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000276:immunology*
C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine