Severe Acute Respiratory Syndrome and the Innate Immune Responses: Modulation of Effector Cell Function without Productive Infection

  • Tseng C
  • Perrone L
  • Zhu H
 et al. 
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Abstract

Severe acute respiratory syndrome (SARS) caused by a novel human coronavirus (CoV), designated SARS-CoV, is a highly contagious respiratory disease with the lungs as a major target. Although the exact mechanism of SARS-CoV pathogenesis remains unknown, an intense, ill-regulated local inflammatory response has been suggested as partially responsible for the devastating lung pathology. We investigated the interaction of SARS-CoV with human macrophages (M{phi}) and dendritic cells (DC), two key innate immune cells of the host immune system, by focusing on their susceptibility to viral infection and subsequent responses (e.g., phenotypic maturation, T cell-priming activity, phagocytosis, and cytokine production). We found neither cell to be permissive for SARS-CoV replication. However, incubation of M{phi} and DC with live, but not gamma irradiation-inactivated, viruses appeared to better sustain their viability. Also, exposure to infectious SARS-CoV led to the phenotypic and functional maturation of DC, with regard to MHC class II and costimulatory molecule expression, T cell-stimulatory capacity, and cytokine production, respectively. Cytokine production was also observed for M{phi}, which were refractory to cell surface phenotypic changes. Strikingly, live SARS-CoV could further prime cell types to respond to a suboptimal dose of bacterial LPS (100 ng/ml), resulting in massive release of IL-6 and IL-12. However, the endocytic capacity (e.g., Ag capture) of M{phi} was significantly compromised upon exposure to infectious SARS-CoV. This study is the first demonstration that although SARS-CoV does not productively infect human M{phi} or DC, it appears to exert differential effects on M{phi} and DC maturation and functions, which might contribute to SARS pathogenesis.

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Authors

  • Chien-Te K Tseng

  • Lucy A Perrone

  • Hongbing Zhu

  • Shinji Makino

  • Clarence J Peters

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