Impaired immune responses following spinal cord injury lead to reduced ability to control viral infection.
Spinal cord injuries disrupt central autonomic pathways that regulate immune function, and increasing evidence suggests that this may cause deficiencies in immune responses in people with spinal cord injuries. Here we analyze the consequences of spinal cord injury (SCI) on immune responses following experimental viral infection of mice. Female C57BL/6 mice received complete crush injuries at either thoracic level 3 (T3) or 9 (T9), and 1 week post-injury, injured mice and un-injured controls were infected with different dosages of mouse hepatitis virus (MHV, a positive-strand RNA virus). Following MHV infection, T3- and T9-injured mice exhibited increased mortality in comparison to un-injured and laminectomy controls. Infection at all dosages resulted in significantly higher viral titer in both T3- and T9-injured mice compared to un-injured controls. Investigation of anti-viral immune responses revealed impairment of cellular infiltration and effector functions in mice with SCI. Specifically, cell-mediated responses were diminished in T3-injured mice, as seen by reduction in virus-specific CD4(+) T lymphocyte proliferation and IFN-γ production and decreased numbers of activated antigen presenting cells compared to infected un-injured mice. Collectively, these data indicate that the inability to control viral replication following SCI is not level dependent and that increased susceptibility to infection is due to suppression of both innate and adaptive immune responses.
Held
Katherine S
KS
Reeve-Irvine Research Center and Department of Anatomy and Neurobiology, University of California, Irvine School of Medicine, 92697-4265, USA.
Steward
Oswald
O
Blanc
Caroline
C
Lane
Thomas E
TE
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D049109:Cell Proliferation; D018352:Coronavirus Infections / Q000276:immunology / Q000401:mortality; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000821:virology; D006517:Murine hepatitis virus; D012367:RNA, Viral / Q000096:biosynthesis; D013119:Spinal Cord Injuries / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000502:physiology; D019562:Viral Load; D014777:Virus Diseases / Q000276:immunology* / Q000401:mortality / Q000473:pathology
D012367:RNA, Viral; D007371:Interferon-gamma