Activation of extracellular pattern recognition receptors by abundant and recurring bacteria in humans

Pattern recognition receptors are an important part of the innate immune system and responsible for identifying pathogenic molecular structures and initiating the immune response by proinflammatory cytokines, chemokines and interferons. One of the most essential pattern recognition receptors are Toll-like receptors that comprise a set of ten subgroups in humans, capable of recognizing a diverse set of conserved bacterial, viral and fungal structures. In this regard, bacterial activation of extracellular Toll-like receptors is of high interest. Recent studies showed that chronic nasal inflammation or viral infection may impact the composition of the host microbiome. Furthermore, an altered microbiome is linked to a variety of diseases and dysregulation of the immune system. For example, allergic disorders in children can be related to a deviated microbiome and changed signaling from Toll-like receptors, possibly resulting from differential exposures to microbes or viral infections. This is the reason why it is essential to understand the interactions of bacteria with the innate immune system and to further decipher altered signaling pathways. To gain insights into the activation profile of Toll-like receptors by bacteria in the human respiratory tract, Toll-like receptor reporter cell lines were used. These cell lines are genetically modified to over-express a human Toll-like receptor and secrete an embryonic alkaline phosphatase upon activation of the respective receptor, which can be quantified photometrically. The selection of bacteria is based on a variety of publications concerning an altered microbiome in context of chronic nasal inflammatory disease or a viral infection. Bacterial species that occurred in an altered amount in ill patients compared to healthy individuals were analyzed. Results showed very distinct activation patterns across all analyzed strains, even within strains of the same species. This demonstrates that the response of Toll-like receptors to each strain must be examined and evaluated independently, since a classification according to a certain species is not necessarily possible. Moreover, there was a significant difference in Toll-like receptor signaling between bacteria that were shown to have a higher or lower prevalence in patients with chronic nasal inflammation. These findings suggest a complex influence from the microbiome on the immune system and disease in humans.