title: Total-Body Irradiation Exacerbates Dissemination of Cutaneous Candida Albicans Infection.
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.
authors.affiliation: Department of a   Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Barlow
authors.affiliation: Department of a   Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Cummings
authors.affiliation: b   Department of Dermatology, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Alice P
authors.initials: AP
authors.lastname: Pentland
authors.affiliation: c   Department of Biostatistics, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Tanzy M T
authors.initials: TM
authors.lastname: Love
authors.affiliation: Department of a   Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Haidaris
authors.affiliation: b   Department of Dermatology, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Julie L
authors.initials: JL
authors.lastname: Ryan
authors.affiliation: Department of a   Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Edith M
authors.initials: EM
authors.lastname: Lord
authors.affiliation: d   Department of Surgery, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Gerber
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000502:physiology* / Q000528:radiation effects; D016207:Cytokines / Q000378:metabolism; D006098:Granulocytes / Q000276:immunology / Q000528:radiation effects; D018664:Interleukin-12 / Q000494:pharmacology; D007668:Kidney / Q000382:microbiology / Q000528:radiation effects; D051379:Mice; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000382:microbiology* / Q000528:radiation effects*; D014916:Whole-Body Irradiation
chemical_list: D016207:Cytokines; D018664:Interleukin-12