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6 October 2016 Total-Body Irradiation Exacerbates Dissemination of Cutaneous Candida Albicans Infection
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Abstract

Exposure to radiation, particularly a large or total-body dose, weakens the immune system through loss of bone marrow precursor cells, as well as diminished populations of circulating and tissue-resident immune cells. One such population is the skin-resident immune cells. Changes in the skin environment can be of particular importance as the skin is also host to a number of commensal organisms, including Candida albicans, a species of fungus that causes opportunistic infections in immunocompromised patients. In a previous study, we found that a 6 Gy sublethal dose of radiation in mice caused a reduction of cutaneous dendritic cells, indicating that the skin may have a poorer response to infection after irradiation. In this study, the same 6 Gy sublethal radiation dose led to a weakened response to a C. ablicans cutaneous infection, which resulted in systemic dissemination from the ear skin to the kidneys. However, this impaired response was mitigated through the use of interleukin-12 (IL-12) administered to the skin after irradiation. Concomitantly with this loss of local control of infection, we also observed a reduction of CD4 and CD8 T cells in the skin, as well as the reduced expression of IFN-γ, CXCL9 and IL-9, which influence T-cell infiltration and function in infected skin. These changes suggest a mechanism by which an impaired immune environment in the skin after a sublethal dose of radiation increases susceptibility to an opportunistic fungal infection. Thus, in the event of radiation exposure, it is important to include antifungal agents, or possibly IL-12, in the treatment regimen, particularly if wounds are involved that result in loss of the skin's physical barrier function.

©2016 by Radiation Research Society.
Margaret L. Barlow, Ryan J. Cummings, Alice P. Pentland, Tanzy M. T. Love, Constantine G. Haidaris, Julie L. Ryan, Edith M. Lord, and Scott A. Gerber "Total-Body Irradiation Exacerbates Dissemination of Cutaneous Candida Albicans Infection," Radiation Research 186(5), 436-446, (6 October 2016). https://doi.org/10.1667/RR14295.1
Received: 20 October 2015; Accepted: 1 July 2016; Published: 6 October 2016
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