Total-Body Irradiation Exacerbates Dissemination of Cutaneous Candida Albicans Infection

• Published in: Radiation research 2016-11, Vol.186 (5), p.436-446
• Main Authors: Barlow, Margaret L., Cummings, Ryan J., Pentland, Alice P., Love, Tanzy M. T., Haidaris, Constantine G., Ryan, Julie L., Lord, Edith M., Gerber, Scott A.
• Format: Article
• Language: English
• Subjects: Animals; Antifungal agents; Barriers; Bone marrow; Candida; Candida albicans; Candida albicans - physiology; Candida albicans - radiation effects; Cytokines - metabolism; Fungi; Fungicides; Granulocytes - immunology; Granulocytes - radiation effects; Immune system; Immune systems; Interleukin-12 - pharmacology; Irradiation; Kidney - microbiology; Kidney - radiation effects; Mice; Populations; Reduction; REGULAR ARTICLES; Skin; Skin (anatomy); Skin - drug effects; Skin - immunology; Skin - microbiology; Skin - radiation effects; Space life sciences; Whole-Body Irradiation
• ISSN: 0033-7587; 1938-5404
• DOI: 10.1667/RR14295.1

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.