Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on Influenza Virus Host Resistance in Mice

Abstract

Kong influenza virus when mice were challenged 7 days after increased susceptibility or severity of infectious disease. An-TCDD administration. Increased mortality was not correlated imal host resistance models that are comparable to and accuwith increased virus titers in the lungs. TCDD at 0.005 or 0.001 rately reflect human diseases are available and have been mg/kg had no effect on influenza-induced mortality. TCDD alone used to assess the effect of TCDD on altered host resistance. did not affect thymus weight at any dose administered in this There are numerous studies indicating that TCDD enhances study. TCDD also did not alter the virus-enhanced increase in susceptibility to bacterial, viral, parasitic, and neoplastic lung weight:body weight ratio nor the virus-induced decrease in challenges.

Aryl Hydrocarbon Receptor Activation Impairs the Priming but Not the Recall of Influenza Virus-Specific CD8+ T Cells in the Lung

“…The difference in the level of suppression in lymphoid organs and lung also suggests that regardless of the magnitude of the CD8 response in lymphoid organs, the immune system has a mechanism for insuring that the site of infection acquires the CD8 ϩ T cells that it needs to successfully eliminate the virus. In fact, we and others (55)(56)(57) have shown previously that there is no difference in the amount of virus in lungs of vehicle control and TCDD-treated mice.…”

“…Although very little is known about the endogenous function of the AhR in the immune system, TCDD has a very profound effect on immune function. In fact, T cell-dependent responses and host resistance to infection are extremely sensitive targets for modulation by AhR agonists (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Although the molecular mechanisms that underlie these effects are not entirely clear, epidemiological data suggest that exposure to pollutants that contain AhR agonists correlates with diminished host resistance, altered immune function, and an increased incidence of influenza and other respiratory infections (27)(28)(29), suggesting a possible cause and effect relationship between exposure to AhR ligands and altered host resistance to infection.…”

Aryl Hydrocarbon Receptor Interacting Protein Targets IRF7 to Suppress Antiviral Signaling and the Induction of Type I Interferon

“…AhR also regulates the host response to virus infection. Treatment of mice with a low dose of the AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin increased morbidity and mortality in mice infected with influenza A virus (69), by impairing the priming of CD8ϩ T cells in the lung (70). Given the broad roles of AhR in the regulation of multiple facets of immune cell development, activation, and differentiation, it will be interesting to determine whether AhR inhibits innate antiviral signaling and type I IFN together with AIP.…”

Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection

“…Myocarditis has been associated with influenza infection in humans (53) and during experimental influenza of mice with mouse-adapted (54,55) or highly pathogenic H5N1 viruses (56), but in our studies cardiac troponin I, a serum marker of myocardial injury, was not elevated at the time of severe disease (data not shown). Thymic atrophy is a common feature of severe infection, including influenza infection (27,37,57), and generally reflects specific depletion of CD4 ϩ CD8 ϩ cortical thymocytes. Several mechanisms may contribute to thymocyte apoptosis; for example, immature CD4 ϩ CD8 ϩ thymocytes are particularly sensitive to induction of apoptosis by glucocorticosteroids that are produced as part of the host's stress response to infection (58).…”