期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 300, 期 2, 页码 L274-L285出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00028.2010
关键词
macrophage; B cell; mesenchymal cell; interstitial lung disease
资金
- National Institutes of Health [HL-087846, AI-065543]
Stoolman JS, Vannella KM, Coomes SM, Wilke CA, Sisson TH, Toews GB, Moore BB. Latent infection by gamma herpesvirus stimulates profibrotic mediator release from multiple cell types. Am J Physiol Lung Cell Mol Physiol 300: L274-L285, 2011. First published October 29, 2010; doi:10.1152/ajplung.00028.2010.-Although gamma herpesvirus infections are associated with enhanced lung fibrosis in both clinical and animal studies, there is limited understanding about fibrotic effects of gamma herpesviruses on cell types present in the lung, particularly during latent infection. Wild-type mice were intranasally infected with a murine gamma herpesvirus (gamma HV-68) or mock-infected with saline. Twenty-eight days postinfection (dpi), similar to 14 days following clearance of the lytic infection, alveolar macrophages (AMs), mesenchymal cells, and CD19-enriched cell populations from the lung and spleen express M-3 and/or glycoprotein B (gB) viral mRNA and harbor viral genome. AMs from infected mice express more transforming growth factor (TGF)-beta(1), CCL2, CCL12, TNF-alpha, and IFN-gamma than AMs from mock-infected mice. Mesenchymal cells express more total TGF-beta(1), CCL12, and TNF-alpha than mesenchymal cells from mock-infected mice. Lung and spleen CD19-enriched cells express more total TGF-beta(1) 28 dpi compared with controls. The CD19-negative fraction of the spleen overexpresses TGF-beta(1) and harbors viral genome, but this likely represents infection of monocytes. Purified T cells from the lung harbor almost no viral genome. Purified T cells overexpress IL-10 but not TGF-beta 1. Intracellular cytokine staining demonstrated that lung T cells at 28 dpi produce IFN-gamma but not IL-4. Thus infection with a murine gamma herpesvirus is sufficient to upregulate profibrotic and proinflammatory factors in a variety of lung resident and circulating cell types 28 dpi. Our results provide new information about possible contributions of these cells to fibrogenesis in the lungs of individuals harboring a gamma herpesvirus infection and may help explain why gamma HV-68 infection can augment or exacerbate fibrotic responses in mice.
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