Microbiota-independent antiviral protection conferred by aminoglycoside antibiotics

Smita Gopinath; Myoungjoo V. Kim; Tasfia Rakib; Patrick W. Wong; Michael van Zandt; Natasha A. Barry; Tsuneyasu Kaisho; Andrew L. Goodman; Akiko Iwasaki

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/248617 doi: bioRxiv preprint but IFN-independent ISG induction has also been reported 24 . We observed increased 248 induction of ISG expression upon neomycin treatment in Ifnar1 -/mice suggesting that 249 IFNAR signaling is dispensable ( Supplementary Fig. 7a ). However, since basal ISG 250 expression was much lower in Ifnar1 -/mice as compared to WT, neomycin treatment only 251 increased gene expression to those of untreated WT mice, thus neomycin treatment was 252 not accompanied by significant antiviral protection ( Supplementary Fig. 7b,c) . Collectively, 253 our results suggest that neomycin induces ISG expression via activation of TLR3-TRIF-254 IRF3/7 signaling pathway to confer protection against HSV-2. Since DCs are required for ISG induction by neomycin, and both monocyte-derived and 293 classical DCs are recruited to the vaginal mucosa, we wondered if TLR3 expression could 294 be used to identify the specific DC subset involved. It is well known that TLR3 is expressed 295 selectively by the cDC1 and not cDC2 (Refs. 26,27 ). Examining TLR3 expression across all 296 DC subsets using the RNA sequencing datasets deposited in the Immunological Genome 297 project 28 confirmed a single cDC subset with high levels of TLR3 expression -CD8a+ 298 author/funder. All rights reserved. No reuse allowed without permission.