Functional disorder of primary immunity responding to respiratory syncytial virus infection in offspring mice exposed to a flame retardant, decabrominated diphenyl ether, perinatally

Abstract

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.

Effect of Brazilian Propolis on Exacerbation of Respiratory Syncytial Virus Infection in Mice Exposed to Tetrabromobisphenol A, a Brominated Flame Retardant

“…It is known that the level of IFN- γ , a Th1 cytokine, in BALF of RSV-infected mice is a sensitive marker of the severity of RSV infection of lungs [11–13, 25]. Thus, we compared the IFN- γ levels in the BALF from RSV-infected mice exposed to TBBPA with and without AF-08 treatment on days 1 and 5 after infection.…”

“…Using this model, perinatal exposure to BFRs has been shown to elevate the levels of IFN- γ in the bronchoalveolar lavage fluid (BALF) of RSV-infected offspring mice with an increase in pulmonary viral titers and exacerbate pneumonia [12, 13], indicating that BFRs are a risk factor for RSV infection across human generations. BFRs are ubiquitously used as industrial materials worldwide.…”

Scientific Opinion on Polybrominated Diphenyl Ethers (PBDEs) in Food

“…Increased virus titres were found in the highest PBDE dose group at 1 and 5 days after infection. This was accompanied by reduced TNFα and IL-6 levels and increased IL-1β secretion one day after infection (Watanabe et al, 2010b).…”

Cytokine dysregulation in autism spectrum disorders (ASD): Possible role of the environment

“…Studies involving marine and murine models link PBDEs to changes in the immune system, including thymic and splenic atrophy, increased production of IL-10, lymphocyte depletion, reduced antibody recall responses, and decreased responses to pathogens (Fowles, Fairbrother et al 1994; Thuvander 1999; Beineke, Siebert et al 2005; Zhou, Chen et al 2006; Beineke, Siebert et al 2007; Beineke, Siebert et al 2007; Lundgren, Darnerud et al 2009; Watanabe, Shimizu et al 2010; Bondy, Lefebvre et al 2011; Fair, Stavros et al 2012). There is little data regarding the impact of PBDEs on cytokine production and signaling, and future studies should examine these endpoints in more detail.…”