Gammaherpesvirus-induced lung pathology is altered in the absence of macrophages

Lung. 2005 Jul-Aug;183(4):239-51. doi: 10.1007/s00408-004-2535-y.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Gammaherpesvirinae*
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / pathology*
  • Lung / pathology*
  • Lung / virology
  • Macrophages, Alveolar / immunology*
  • Macrophages, Alveolar / pathology
  • Mice
  • Mice, Inbred BALB C
  • Receptors, CCR2
  • Receptors, Chemokine / immunology*

Substances

  • Ccr2 protein, mouse
  • Receptors, CCR2
  • Receptors, Chemokine