Journal
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Volume 311, Issue 3, Pages L611-L627Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00193.2016
Keywords
BMT; CCR2; fibrosis; herpesvirus; IL17
Categories
Funding
- NIH [AI117229, HL115618]
- [T32HL07749]
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CCR2-expressing leukocytes are required for the progression of fibrosis in models of induced lung injury as well as models of bone marrow transplant (BMT)-related idiopathic pneumonia syndrome. Infection with murid gamma-herpesvirus-68 (gamma HV-68) results in severe pneumonitis and pulmonary fibrosis following syngeneic BMT; however, the roles that various proinflammatory leukocyte populations play in this process remain unclear. Deletion of CCR2 in both non-BMT and BMT mice increased early lytic viral replication and resulted in a reduction in the numbers of lung-infiltrating GR1 +,F4/80+ and CXCR1+ cells, while maintaining robust neutrophil infiltration. Similarly, in gamma HV-68-infected CCR2(-/-) BMT mice, recruitment of monocytes and lymphocytes were reduced whereas neutrophil recruitment was increased compared with wild-type (WT) BMT mice. Interestingly, levels of profibrotic IL-17 were increased in infected CCR2 BMT mice compared with WT BMT. Furthermore, an increase in lung-associated collagen was detected even though there was an overall decrease in the number of profibrotic CCR2+ fibrocytes detected in the lungs of CCR2(-/-) BMT mice. These data indicate that, contrary to most models of fibrosis, deletion of CCR2 offers no protection from gamma-herpesvirus-induced pneumonitis and fibrosis, and, indeed, CCR2+ cells play a suppressive role during the development of pulmonary fibrosis following gamma-herpesvirus infection post-BMT by limiting IL-7 and collagen production.
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