Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone

PLoS Pathogens

Ashok Srinivasan¹  Heba H. Mostafa²  Peter Vogel³  Charles J. Russell⁴ 

[1] Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children’s Research Hospital, Memphis, Tennessee, United States of America;Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, United States of America;Department of Pathology, St. Jude Children’s Research Hospital, Memphis, Tennessee, United States of America;Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America

关键词: Neutrophils;    Respiratory infections;    T cells;    Drug therapy;    Bioluminescence;    Viral clearance;    Antibodies;    Lymphocytes;   

DOI  :  10.1371/journal.ppat.1005875

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus—specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential.

【 授权许可】

CC BY