An immunocompromised BALB/c mouse model for respiratory syncytial virus infection.
BACKGROUND
Respiratory syncytial virus (RSV) infection causes bronchiolitis in infants and children, which can be fatal, especially in immunocompromised patients. The BALB/c mouse, currently used as a model for studying RSV immunopathology, is semi-permissive to the virus. A mouse model that more closely mimics human RSV infection is needed. Since immunocompromised conditions increase risk of RSV infection, the possibility of enhancing RSV infection in the BALB/c mouse by pretreatment with cyclophosphamide was examined in this study. BALB/c mice were treated with cyclophosphamide (CYP) and five days later, they were infected with RSV intranasally. Pulmonary RSV titers, inflammation and airway hyperresponsiveness were measured five days after infection.


RESULTS
CYP-treated mice show higher RSV titers in their lungs of than the untreated mice. Also, a decreased percentage of macrophages and an increased number of lymphocytes and neutrophils were present in the BAL of CYP-treated mice compared to controls. The CYP-treated group also exhibited augmented bronchoalveolar and interstitial pulmonary inflammation. The increased RSV infection in CYP-treated mice was accompanied by elevated expression of IL-10, IL-12 and IFN-gamma mRNAs and proteins compared to controls. Examination of CYP-treated mice before RSV infection showed that CYP treatment significantly decreased both IFN-gamma and IL-12 expression.


CONCLUSIONS
These results demonstrate that CYP-treated BALB/c mice provide a better model for studying RSV immunopathology and that decreased production of IL-12 and IFN-gamma are important determinants of susceptibility to RSV infection.
Kong
Xiaoyuan
X
Department of Internal Medicine, Division of Allergy and Immunology, Joy McCann Culverhouse Airway Disease Research Center, University of South Florida College of Medicine, USA. xkong@hsc.usf.edu
Hellermann
Gary R
GR
Patton
Geoff
G
Kumar
Mukesh
M
Behera
Aruna
A
Randall
Timothy S
TS
Zhang
Jian
J
Lockey
Richard F
RF
Mohapatra
Shyam S
SS
D000818:Animals; D001835:Body Weight; D003520:Cyclophosphamide / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D016867:Immunocompromised Host / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000502:physiology*
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D003520:Cyclophosphamide