Doss, Argenia et al. (2015) International Worm Meeting "Neural regulation of innate immune response using optogenetics."

Doss, Argenia, Aballay, Alejandro

[International Worm Meeting, 2015]

Previously, our laboratory showed that OCTR-1, a G protein-coupled catecholamine receptor, suppresses the innate immune response in Caenorhabditis elegans. As a result, animals expressing the loss-of-function octr-1 allele, ok371, exhibited an enhanced resistance to killing by the human opportunistic pathogen Pseudomonas aeruginosa. Despite OCTR-1 being expressed in five neurons, data from our laboratory suggests that OCTR-1 functions in chemosensory neurons ASI and/or ASH to suppress innate immunity. However, the specific role of ASI and ASH neurons is unclear. Unpublished data from our laboratory showed that ASI neurons do not affect the susceptibility of C. elegans to P. aeruginosa. Therefore, we examined the role of ASH neurons during infection. With the use of optogenetics, we were able to assess whether activation of ASH neurons via Channelrhodopsin-2 alters the susceptibility of C. elegans to P. aeruginosa-mediated killing. Preliminary data from our experiments revealed that activation of ASH neurons during exposure to P. aeruginosa alters the susceptibility of C. elegans to P. aeruginosa-mediated killing. This suggests that ASH neurons can regulate the innate immune response in C. elegans and OCTR-1 may suppress innate immunity by acting through ASH neurons. Ongoing experiments are directed towards determining how ablation of ASH neurons and OCTR-1 expression in ASH neurons alters immune response. Currently, our data suggests that ASH neurons, and less likely ASI neurons, possess an immunoregulatory function. Data from these studies will help clarify the cellular process(es) involved in OCTR-1's regulation of innate immune response in C. elegans.

Doss, Argenia L. et al. (2013) International Worm Meeting "Role of OCTR-1 expressing neurons during pathogen infection."

Aballay, Alejandro, Doss, Argenia L.

[International Worm Meeting, 2013]

Recent studies from our laboratory showed that OCTR-1, a G protein-coupled catecholamine receptor, down-regulates genes required for innate immunity. Thus, octr-1(ok371) animals exhibit enhanced resistance to killing by the human opportunistic pathogen Pseudomonas aeruginosa. While OCTR-1 is expressed in five neurons, data suggest that OCTR-1 functions in chemosensory neurons ASI and/or ASH to suppress innate immunity. However, the specific role of ASI and ASH neurons is unclear. Therefore, we examined the role of ASI neurons during infection by measuring the susceptibility of an ASI-ablated strain to P. aeruginosa-mediated killing. Our experiments revealed that animals lacking ASI neurons exhibited enhanced susceptibility to P. aeruginosa-mediated killing when compared to wild-type animals, indicating that ASI is protective against infection. Genetic ablation of ASI cells also suppresses the enhanced resistance to P. aeruginosa-mediated killing of octr-1(ok371) animals, suggesting that OCTR-1 may suppress innate immunity by inhibiting ASI neurons. Ongoing experiments to determine the immune function of animals expressing OCTR-1 in ASH or ASI neurons will help us to further address the role of ASI and ASH neurons during pathogen infection. Thus far, our data suggest a role for ASI neurons in the control of innate immunity and further elucidates the mechanism by which OCTR-1 regulates the process.