Pseudomonas Aeruginosa Inducing Nociception Increases Susceptibility to Bacterial Keratitis

nociception;TRPV1;CGRP Pseudmonas aeruginosa;Type IV pili;neutrophils

Lin, Tiffany

University:Havard University

Department:Biology

关键词: nociception;    TRPV1;    CGRP Pseudmonas aeruginosa;    Type IV pili;    neutrophils;   

Others  :  https://dash.harvard.edu/bitstream/handle/1/42004075/LIN-DOCUMENT-2019.pdf?sequence=1&isAllowed=y

美国|英语

来源: Digital Access to Scholarship at Harvard

【 摘 要 】

Understanding nociceptive signaling during Pseudomonas keratitis and its impact on the immune response can prove to be useful for this very painful infection. While the cornea is one of the mostly densely innervated organs in the body, the role that nociception has during bacterial keratitis has yet to be elucidated. In this study, I utilize a novel experimental mouse model, using systemic treatment of Resiniferatoxin (RTX), a potent capsaicin analog that ablates TRPV1 positive neurons to assess the role of sensory neurons during Pseudomonas keratitis. While this model has been used to study lung, skin and gut pathologies, it has yet be confirmed whether this would prove to be useful in the context of the eye. Treated mice were used for an in vivo bacterial keratitis experiment to assess the impact that sensory neurons have on bacterial clearance and inflammation. Using in vitro experiments such as calcium imaging of primary trigeminal ganglia neurons, I assessed whether the pathogen can directly activate neurons depending on virulence factors. My results demonstrate that nociceptors can be directly activated by Pseudomonas and mediate immune response to infection. This could be due to CGRP, where we found that the presence of the neuropeptide impeded neutrophil dependent bacterial killing and reduced bacterial clearance in mice.