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Neutrophils promote mononuclear cell infiltration during viral-induced encephalitis
Jiehao Zhou1, Stephen A Stohlman, David R Hinton
1Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Abstract:
Neutrophils are the first infiltrating cell population to appear within the CNS during infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV). To determine whether neutrophils play a role in limiting acute JHMV infection, mice were depleted of neutrophils. Infection of neutropenic animals resulted in increased levels of virus replication and mortality compared with control mice. Furthermore, neutropenia resulted in significantly reduced mononuclear leukocyte infiltration possibly due to reduced loss of blood brain barrier integrity during acute JHMV infection. These data suggest that infiltrating neutrophils are crucial for limiting virus replication during acute JHMV infection, contribute to the loss of blood brain barrier integrity and play a role in shaping adaptive immunity within the CNS.
Insights
Neutrophils are vital in fighting mouse hepatitis virus (JHMV) infection in the central nervous system (CNS). Depleting neutrophils worsened JHMV replication and mortality, highlighting their protective role.
Area of Science:
- Neuroimmunology
- Virology
- Infectious Disease
Background:
- Neutrophils are the initial immune cells to infiltrate the central nervous system (CNS) during JHMV infection.
- The precise role of neutrophils in acute JHMV infection remains unclear.
Purpose of the Study:
- To investigate the role of neutrophils in limiting acute JHMV infection.
- To understand neutrophil involvement in CNS pathology and adaptive immunity during JHMV infection.
Main Methods:
- Neutrophil depletion in mice prior to JHMV infection.
- Quantification of viral replication and mortality rates.
- Assessment of blood-brain barrier integrity and immune cell infiltration.
Main Results:
- Neutropenic mice exhibited significantly increased JHMV replication and mortality compared to control groups.
- Reduced infiltration of mononuclear leukocytes was observed in neutropenic mice.
- Neutrophil depletion correlated with reduced blood-brain barrier disruption.
Conclusions:
- Infiltrating neutrophils are critical for controlling JHMV replication during acute infection.
- Neutrophils contribute to blood-brain barrier integrity loss and influence adaptive immune responses within the CNS.