New research published in the Journal of Investigative Dermatology and released by Elsevier on Apr. 16 reveals that keratinocytes, or skin cells, can support replication of the rabies virus and transmit it to neurons. The study provides direct evidence that even minor scratches or bites from dogs and bats could lead to neuroinvasion, increasing the risk of infection.
Rabies is a deadly zoonotic disease causing at least 59,000 human deaths annually worldwide. While most infections are caused by dog bites, experts have long been concerned about superficial exposures such as bat scratches or minor wounds. Until now, the mechanism behind these risks was not well understood.
Lead investigator Corine H. Geurts van Kessel said: "In our previous work, we discovered that keratinocytes-cells that form the epidermis, the outermost layer of the skin-were infected at the site of entry of the rabies virus, both in natural and experimental infections. This was unexpected, as rabies pathogenesis has traditionally focused on muscle cells and motor neurons." The research team used primary human keratinocyte cultures to examine susceptibility to three different strains of rabies virus: a vaccine strain and two wild-type strains from fatal cases involving bats and dogs.
The findings showed that while a dog-associated strain led to minimal infection in keratinocytes with limited immune response activation, other strains infected these cells more easily and triggered strong antiviral responses. A co-culture model developed for this study demonstrated successful transmission from infected keratinocytes directly to adjacent neurons—suggesting a pathway for neuroinvasion through superficial wounds.
Co-investigator Keshia Kroh said: "Our study demonstrates that the skin might play a more important role in rabies infection than previously recognized. We were particularly surprised by the strong antiviral response mounted by keratinocytes to the bat-related rabies virus strain." She added that this raises new questions about how immune responses originating from skin cells affect disease progression.
Carmen W.E. Embregts noted: "Our study provides a biological rationale for these recommendations... Awareness that superficial skin exposures can represent a route of neuroinvasion helps ensure that potential risks are recognized and evaluated appropriately..."
JID Associate Editor Ethan Lerner observed: "The data in this study support the increasingly recognized concept that cells in the skin are in snug communication with the nervous system. That a scratch or bite is needed for transmission of rabies is further evidence of importance of an intact skin barrier in health."
