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Human parechovirus and enterovirus initiate distinct CNS innate immune responses: Pathogenic and diagnostic
Danielle Fortuna1, Ana María Cárdenas2, Erin H Graf2
1Thomas Jefferson University Hospital, Pathology, Philadelphia, PA, United States.
Background:
Human parechovirus (HPeV) and enterovirus (EV) cause a range of human diseases including serious CNS infections. Little is known regarding the immune response to HPeV meningitis compared to EV meningitis or how the immune response to HPeV reflects its pathogenesis.
Objective:
To characterize the innate immune response to HPeV CNS infection in order to increase our understanding of HPeV pathogenesis and possibly help identify HPeV in the clinical setting.
Study Design:
CSF samples from 13 patients with HPeV meningitis, 7 patients with EV meningitis, and 11 patients negative for CNS infections were analyzed for chemokines/cytokines using multiplex ELISA assays.
Results:
CSF levels of the majority of cytokines/chemokines analyzed were significantly higher in patients with EV meningitis (EV group) compared to patients with HPeV meningitis (HPeV group) and controls. In the HPeV group, a small number of cytokine/chemokine levels were higher than controls; however, these levels were either significantly lower or not significantly different compared to the EV group. IL-6 levels were lower in HPeV than in both EV and controls.
Conclusions:
The immune response to HPeV CNS infection differs from that of EV. Distinct patterns of cytokine/chemokine expression in HPeV infections suggest HPeV-mediated modulation of the immune response. HPeV disrupts the interferon cascade and seems to interfere with early inflammatory signaling. Although HPeV elicits a predominantly muted immune reaction, a partial, general infectious-type cytokine/chemokine response does occur. Beyond providing insight into HPeV pathogenesis, the identified cytokine/chemokine profile may aid in early detection of HPeV infection.
Insights
Human parechovirus (HPeV) meningitis shows a muted immune response compared to enterovirus (EV) meningitis. Understanding these distinct cytokine profiles aids in HPeV infection detection and pathogenesis insights.
Area of Science:
- Neurovirology
- Immunology
- Infectious Diseases
Background:
- Human parechovirus (HPeV) and enterovirus (EV) are significant causes of central nervous system (CNS) infections.
- The immune response to HPeV meningitis is poorly understood compared to EV meningitis.
- Clarifying HPeV's immune response is crucial for understanding its pathogenesis.
Purpose of the Study:
- To characterize the innate immune response to HPeV CNS infections.
- To enhance understanding of HPeV pathogenesis.
- To identify potential biomarkers for early HPeV detection.
Main Methods:
- Analysis of cerebrospinal fluid (CSF) from patients with HPeV meningitis, EV meningitis, and controls.
- Utilized multiplex ELISA assays to measure cytokine and chemokine levels.
- Compared immune mediator profiles across the three groups.
Main Results:
- CSF cytokine/chemokine levels were significantly higher in EV meningitis patients than in HPeV meningitis patients and controls.
- HPeV meningitis showed a muted inflammatory response compared to EV meningitis.
- Interleukin-6 (IL-6) levels were lower in HPeV meningitis compared to both EV meningitis and controls.
Conclusions:
- The immune response to HPeV CNS infection is distinct from EV infections, indicating HPeV-mediated immune modulation.
- HPeV appears to disrupt the interferon cascade and early inflammatory signaling.
- The identified cytokine/chemokine profile may assist in the early clinical detection of HPeV infections.
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