The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling

• DOI: 10.7554/elife.47117
• Publication Date: 2019-07-16T00:00:20Z
• Authors: D Garrett Brown; Raymond Soto; Soumya Yandamuri; Colleen Stone; Laura Dickey; Joao Carlos Gomes...; Elissa D Pastuzyn; Rickesha Bell; Charisse Petersen; Kaitlin Buhrke; Robert S Fujinami; Ryan M O'Connell; W Zac Stephens; Jason D Shepherd; Thomas E Lane; June L Round
• Keywords: Gut–brain axis

Symbiotic microbes impact the function and development of central nervous system (CNS); however, little is known about contribution microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function. Germfree mice or animals receive antibiotics are unable to control viral replication within brain leading increased paralysis. Microglia derived from germfree antibiotic-treated cannot stimulate viral-specific immunity depletion leads worsened demyelination. Oral administration toll-like receptor (TLR) ligands virally infected limits Homeostatic activation dependent on intrinsic signaling TLR4, as disruption TLR4 microglia, but not entire CNS (excluding microglia), clinical disease. This work demonstrates gut immune-stimulatory products can influence prevent damage infection.