Our lungs are the largest interface between the human host and the external environment, being exposed to more than 8 000 litres of inhaled air each day. Although not visible by the naked eye, the air is teeming with bacteria. Inevitably, these bacteria are frequent visitors of our respiratory system. Although exposure to microbes and their components has been shown to be important for the development of our immune system (hygiene hypothesis). What happens when we are in an urban environment- exposed to microbes and pollutants simultaneously?
By now, we all know about air pollution – the world's largest environmental health risk. The World Health Organization (WHO) estimates that in 2012 air pollution caused one in eight of total global deaths, being linked to stroke, heart disease, lung cancer, and both chronic and acute respiratory diseases, including asthma. However, air pollution not only affects our health, but also our quality of living. Nationally, Belgium is an important hotspot for traffic-related air pollution, with particulate air pollution being one of the highest of Western Europe.
The pollutant most associated with the health effects is particulate matter, a heterogeneous mixture of liquid and solid materials suspended in the air, and typically small enough (<10μm) to be respired. Mechanistic studies indicate that the observed health effects are related to the capacity of inhaled PM to induce oxidative stress and airway inflammation. There is conflicting evidence in the literature as to the predominant mechanisms and also the compositional element(s) that drive the inflammatory response of ambient PM. Although PM consists of a very complex mixture, of these components, bacterial endotoxins (or lipopolysaccharides) from the cell wall of Gram-negative bacteria are well-known for their high pro-inflammatory capacity. To attribute their role in PM-related inflammation, we need to know if endotoxins are present in an urban environment?
Subsequently, several global studies have monitored ambient endotoxin concentrations in an urban environment, however they reported very low concentrations, thus discouraging their importance in an urban environment, and thus their involvement in PM-related inflammation. We investigated the methods used in all these studies and found that they relied on filter-based collection strategies which are typically used to collect PM. However, the problem with these methods is that once the endotoxins are captured on the filter, they are very difficult to remove for analysis. Improving on these methods, our study used an impinger-based strategy, depositing the airborne endotoxins directly into water, obtaining more than 30 fold higher endotoxin concentrations.
Now that we know that endotoxins are indeed in significant concentrations within an urban environment, it urges us to re-evaluate their role in PM-related inflammation.
Briefly, we will i) monitor spatiotemporal endotoxin concentrations by applying novel and up-to-date methods, and utilizing colony sequencing to identify possible sources for endotoxin increases within an urban environment; ii) elucidate the contribution of microbial endotoxins in PM-associated inflammation using human respiratory cell lines models, as well as to investigate any synergistic effects with other PM components by using synthetic pollutant models iii) gain mechanistic insights into inflammatory pathways and regulation of key receptors using RT qPCR, dedicated PCR arrays or RNA seq, iv) validating some of our findings in human volunteers from nasal brushings upon short-term PM exposure.