Abstract
Presentation Description :
It has long been considered that a neutrophil’s response to various infectious challenges is innately pre-determined. Here, we provide data that demonstrates that neutrophil transcriptomes and proteomes are modulated by the microbiota. Using RNAseq and quantitative proteomic approaches we defined mature neutrophil transcriptome and proteome signatures at steady state and during ocular infection with Pseudomonas aeruginosa. We found that the proteomic signatures of mature neutrophils derived from the GF and SPF were significantly different. GF-serum exposed neutrophil progenitors did not mature efficiently and had compromised bactericidal properties when compared to progenitors matured in SPF-derived serum. To identify molecular pathways, we set-up an in vitro system where neutrophil progenitors were transduced with lenti-guides to knock-down key microbiota-driven pathway gene targets. We are currently examining the maturation and bactericidal characteristics of “CRISPR-ed” neutrophils. We will present data on newly identified, previously not studied molecules that regulate neutrophil bactericidal properties.
Cumulatively, the data support the concept that microbiota affects neutrophil maturation by defining not only the quantity, but also the quality of mature neutrophils. We predict that neutrophil responses can be specifically tailored to pathogens. In conclusion, neutrophil responses, although innately determined, are adapted and molded by the commensal presence.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.