Abstract
Many persistent organic pollutants, such as polychlorinated biphenyls (PCBs), have high immunomodulating potentials. Exposure to them, in combination with virus infections, has been shown to aggravate outcomes of the infection, leading to increased viral titers and host mortality. Expression of immune-related microRNA (miR) signaling pathways (by host and/or virus) have been shown to be important in determining these outcomes; there is some evidence to suggest pollutants can cause dysregulation of miRNAs. It was thus hypothesized here that modulation of miRNAs (and associated cytokine genes) by pollutants exerts negative effects during viral infections. To test this, an in vitro study on chicken embryo fibroblasts (CEF) exposed to a PCB mixture (Aroclor 1260) and then stimulated with a synthetic RNA virus (poly(I:C)) or infected with a lymphoma-causing DNA virus (Gallid Herpes Virus 2 [GaHV-2]) was conducted. Using quantitative real-time PCR, expression patterns for mir-155, pro-inflammatory TNFα and IL-8, transcription factor NF-κB1, and anti-inflammatory IL-4 were investigated 8, 12, and 18 h after virus activation. The study showed that Aroclor1260 modulated mir-155 expression, such that a down-regulation of mir-155 in poly(I:C)-treated CEF was seen up to 12 h. Aroclor1260 exposure also increased the mRNA expression of pro-inflammatory genes after 8 h in poly(I:C)-treated cells, but levels in GaHV-2-infected cells were unaffected. In contrast to with Aroclor1260/poly(I:C), Aroclor1260/GaHV-2-infected cells displayed an increase in mir-155 levels after 12 h compared to levels seen with either individual treatment. While after 12 h expression of most evaluated genes was down-regulated (independent of treatment regimen), by 18 h, up-regulation was evident again. In conclusion, this study added evidence that mir-155 signaling represents a sensitive pathway to chemically-induced immunomodulation and indicated that PCBs can modulate highly-regulated innate immune system signaling pathways important in determining host immune response outcomes during viral infections.
Highlights
Persistent organic pollutants (POPs) like polychlorinated biphenyls (PCBs) and their Arochlor (Ars) commercial mixtures are known to interfere with immune signaling pathways (Safe 1994; Olsen 2005)
Thereafter, the treatment groups were cells exposed to Ar1260 (22.23 ppm dissolved in corn oil; this concentration was chosen based on preliminary experiments done to attain a sublethal concentration in the chicken embryo fibroblasts (CEF)) and control cells that received vehicle only
One can describe how presence of multiple stressors significantly modulate natural immune responses of hosts infected with RNA (poly(I:C)) or DNA (GaHV-2) virus
Summary
Persistent organic pollutants (POPs) like polychlorinated biphenyls (PCBs) and their Arochlor (Ars) commercial mixtures are known to interfere with immune signaling pathways (Safe 1994; Olsen 2005). POP production increased until the 1980s when most were banned or regulated on a national basis (Wo€hrnschimmel et al 2016) These persistent compounds are still found today in the environment and in biota. A peak in the incidence in infectious diseases between 1940 and 2004 was found in the 1980s (74.4% virus and bacteria); this was mainly associated with an increased susceptibility of the host to infections (Jones et al 2008) These corresponding peaks (pollutants and pathogens) could indicate an involvement of POPs in outbreaks of infectious diseases; this further underlines the need for a closer investigation of the immune system of hosts under continuing exposures to POPs. The innate immune system represents the first line of defense in a host against pathogens; modulation of these pathways is known to be detrimental (Muralidharan and Mandrekar 2013)
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