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Viral induction of low frequency interferon-alpha producing cells
S B Feldman1, M Ferraro, H M Zheng
1Department of Laboratory Medicine and Pathology, University of Medicine and Dentistry of New Jersey, Newark 07103.
Virology
|October 1, 1994
Summary
Most human interferon-alpha (IFN-alpha) production comes from low-frequency, non-monocytic cells, not monocytes, across various viral stimuli. This finding challenges previous assumptions about IFN-alpha-producing cells (IPC).
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human interferon-alpha (IFN-alpha) production is crucial for antiviral responses.
- IFN-alpha-producing cells (IPC) were previously identified as monocytes or a distinct light density, HLA-DR+ population.
- The frequency of IPC varies significantly depending on the viral stimulus (e.g., Sendai virus vs. Herpes simplex virus [HSV]).
Purpose of the Study:
- To comprehensively characterize the frequency and nature of IPC responding to a broad range of DNA and RNA viruses.
- To investigate the role of chloroquine sensitivity in distinguishing IPC populations.
- To determine the primary cell type responsible for IFN-alpha production against diverse viral challenges.
Main Methods:
- ELISpot assays were employed to quantify IPC frequencies against various viruses (HSV, Sendai, vesicular stomatitis virus, cytomegalovirus, adenovirus, SV40, influenza, measles, mumps, Newcastle disease virus [NDV], and human immunodeficiency virus [HIV]).
- Enveloped and non-enveloped viruses were tested for their ability to elicit IFN-alpha responses.
- Sensitivity of IPC to chloroquine treatment was assessed to differentiate cell populations.
Main Results:
- Enveloped viruses, but not non-enveloped viruses (adenovirus, SV40), induced IFN-alpha production.
- The frequency of IPC for most tested viruses was comparable to the low-frequency HSV-responding population, not the high-frequency Sendai virus response.
- Chloroquine treatment abrogated most IFN-alpha production, except for Sendai virus, indicating distinct cellular mechanisms.
Conclusions:
- The majority of IFN-alpha production in response to diverse viral stimuli originates from low-frequency, non-monocytic IPC.
- This contrasts with the traditional view of monocytes as the primary IFN-alpha producers for certain viruses.
- The findings highlight the heterogeneity of IPC and their distinct responses to different viral types and treatments.