Radiation-induced depletion of cutaneous dendritic cells: Functional consequences of a breakdown in the cutaneous immunological barrier (P4259)

The United States continues to be a prime target for attack by terrorist organizations in which nuclear detonation or dispersal of radiological material are legitimate threats. These types of attacks could result in devastating consequences to a multitude of individuals in the form of radiation injury to particular organ systems. One of these organs, the cutaneous system, which provides the first line of defense against invading pathogens, is particularly sensitive to ionizing radiation (IR) leaving the host vulnerable to cutaneous pathogen invasion. Our laboratory demonstrated that exposure to IR depleted murine cutaneous dendritic cells (cDCs); a network of cells responsible for forming a cutaneous immunological barrier that is critical in protecting the host against microorganism infection. This IR-induced depletion was caused by a migration of cDCs out of the skin responding to abnormal upregulation of cDC migratory factors, CCR7 and CCL21. As a result, this breakdown in the immunological barrier left the host susceptible to a cutaneous Candida albicans challenge where the pathogen was not contained locally but rather disseminated systemically to the kidneys. Interestingly, a subcutaneous treatment with IL-12 prevented the IR-induced depletion of cDCs offering a potential radiation countermeasure to preserve the cutaneous immunological barrier and perhaps prevent the lethal dissemination of opportunistic pathogens following radiation exposure.