title: 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.
abstract: 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.
authors: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
authors: Heba H
authors: HH
authors: Mostafa
authors: Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
authors: Peter
authors: P
authors: Vogel
authors: Department of Bone Marrow Transplantation and Cellular Therapy, 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.
authors: Ashok
authors: A
authors: Srinivasan
authors: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.|Department of Microbiology, Immunology & Biochemistry, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors: Charles J
authors: CJ
authors: Russell
mesh_terms: D000818:Animals; D003520:Cyclophosphamide / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006801:Humans; D016867:Immunocompromised Host; D007694:Killer Cells, Natural / Q000276:immunology / Q000821:virology; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000473:pathology / Q000821:virology; D018184:Paramyxoviridae Infections / Q000276:immunology* / Q000821:virology; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D010253:Respirovirus Infections / Q000188:drug therapy / Q000276:immunology / Q000473:pathology* / Q000821:virology; D029082:Sendai virus / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D000069585:Filgrastim