Functional disorder of primary immunity responding to respiratory syncytial virus infection in offspring mice exposed to a flame retardant, decabrominated diphenyl ether, perinatally.
Perinatal exposure to a representative flame retardant, decabrominated diphenyl ether (DBDE), was shown previously to increase viral titers in the lungs of respiratory syncytial virus (RSV)-infected offspring on day 5 post-infection, resulting in exacerbation of pneumonia. In this study, the significant increase of pulmonary viral titers was confirmed even on day 1 post-infection and the effect on the primary immune response to RSV infection were examined to assess a mode of DBDE action on developmental immunotoxicity. On day 1 after infection, the secretion of both TNF-alpha and IL-6 decreased significantly in the bronchoalveolar lavage fluid prepared from RSV-infected offspring exposed to DBDE perinatally, but IL-1beta increased. However, in ex vivo lipopolysaccharide stimulation test, the productivity of TNF-alpha in the bronchoalveolar lavage cells, which are mainly primary immune cells responding to RSV infection, prepared from offspring mice exposed to DBDE perinatally was not lower than that in the control. The primary immune cells retained normally the ability of cytokine production after the DBDE exposure. Gene expressions of innate pattern recognition receptors (Toll-like receptor 3 and 4, melanoma differentiation-associated gene-5, and retinoic acid-inducible gene I) in lung tissues were not affected by DBDE exposure. Because the levels of TNF-alpha, IL-6, and IL-1beta are known to be elevated in the lungs of RSV-infected mice, these irregular productions due to perinatal DBDE exposure indicate a disorder of the primary immune response to RSV infection. Thus, perinatal exposure to DBDE was suggested to cause a functional disorder of primary immunity responding to RSV infection.
Watanabe
Wataru
W
Department of Microbiology, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Nobeoka, Miyazaki, Japan.
Shimizu
Tomomi
T
Sawamura
Rie
R
Hino
Akane
A
Konno
Katsuhiko
K
Kurokawa
Masahiko
M
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis; D005260:Female; D005411:Flame Retardants / Q000633:toxicity*; D007113:Immunity, Innate / Q000187:drug effects*; D007155:Immunologic Factors / Q000633:toxicity*; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D010647:Phenyl Ethers / Q000633:toxicity*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*
D016207:Cytokines; D005411:Flame Retardants; D007155:Immunologic Factors; D010647:Phenyl Ethers; C031538:phenyl ether