2024 AIChE Annual Meeting

Airway Prevotella Promote Inhibition of Streptococcus Pneumoniae Infection through Chemokine and Neutrophil Modulation

The human body is host to many naturally occurring (commensal) bacteria as part of individualized microbiota varying in composition by anatomical location and throughout one’s life. These bacterial communities play a crucial role in host-pathogen interactions and the immune response, both through direct harming of pathogens as well as regulation of immune signaling pathways. Prevotella species are highly prevalent components of these communities, including within the respiratory microbiota. Streptococcus pneumoniae, a notable respiratory pathogen, is the leading cause of community acquired pneumonia, and the largest infectious cause of death in children under 5 years of age. Furthermore, pneumococcal vaccines are more protective against invasive pneumococcal infections rather than lung infections, emphasizing the need to identify other therapeutics as well as risk factors for pneumococcal pneumonia. This study investigates how specific Prevotella species can regulate early immune responses to respiratory infection by S. pneumoniae, with the aim of utilizing this knowledge to generate novel immunotherapies.

Investigation of Prevotella’s effects on the presence of common chemokines such as CXCL2 and IL-8 revealed a marked increase of chemokine secretion after A549 and D562 (respiratory epithelial cells from the lung and pharynx respectively) were inoculated to Prevotella melaninogenica. Furthermore, flow cytometry studies of mouse lung and bronchoalveolar lavage (BAL) samples showed an increase in neutrophil percentage and total recruitment in response to P. melaninogenica inoculation. Lastly, adherence and infection assays demonstrated increased abundance of P. melaninogenica correlates with reduced infection by S. pneumoniae, whereas increased abundance of P. intermedia correlates with increased infection by S. pneumoniae. Together, these findings suggest innate immune priming behaviors of the respiratory microbiota by P. melaninogenica through chemokine and neutrophil modulation help to reduce S. pneumoniae infection. Furthermore, future investigations into P. intermedia’s behavior are warranted to better understand what signaling causes upregulation of S. pneumoniae infection. With a heightened knowledge of these commensal mechanisms, we seek to harness these regulatory pathways to allow the creation of translational therapies aiming to mitigate and prevent pneumonia worldwide.