ABSTRACT
Irradiation of skin by ultraviolet radiation in mice and humans leads to a suppression of cell-mediated immunity. This process is initiated when one of the photoreceptors in skin, trans-urocanic acid, is photoisomerized to cis-urocanic acid, an immunomodulator. High levels of L-histidine, histamine, and trans-urocanic acid are found in humans and animals when they are protein malnourished. Mice fed on an elevated L-histidine diet have more trans-urocanic acid in the skin and are more susceptible to UV-induced immune suppression. Sojourners to high altitudes are malnourished, suffer protein catabolism, are exposed to sun, and often acquire infectious diseases. There is evidence that sunscreens may not adequately protect the immune system. Furthermore, UV intensity increases with altitude. We propose a testable hypothesis: UV radiation causes photoimmune suppression in sojourners to high altitude and this allows infectious diseases to develop. The mechanism we propose includes protein malnutrition, high levels of trans-urocanic acid, ultraviolet radiation, formation of cis-urocanic acid, immune suppression, and infection.
Subject(s)
Immunosuppression Therapy , Mountaineering/physiology , Nutrition Disorders , Protein Deficiency/complications , Ultraviolet Rays/adverse effects , Urocanic Acid/adverse effects , Altitude , Animals , Communicable Diseases/etiology , Female , Humans , Male , Mice , Risk Factors , Urocanic Acid/pharmacologyABSTRACT
UV-B radiation suppresses cell-mediated immunity. Histidine forms trans-urocanic acid (trans-UCA) enzymatically in the stratum corneum. Photoisomerization of trans-UCA to cis-urocanic acid (cis-UCA) has been proposed for the initiation of an immunosuppressive process. Many microorganisms described in the literature metabolize histidine and/or trans-UCA. Our enrichment cultures of soil and sewage contain organisms that can degrade cis-UCA. We have tested microorganisms for degradation of cis-UCA, trans-UCA, or L-histidine when they are incorporated at 0.2% in nutrient broth. Six out of 10 selected genera isolated by our clinical microbiology laboratory degrade one or more of the imidazole substrates. We have cultured over 60 aerobic isolates from human skin. Of these, 33 degrade one or more of the three imidazole substrates and 12 degrade cis-UCA. Isolates from BALB/c mice are also active on cis-UCA. We have identified a cis-UCA-degrading bacterium as Micrococcus luteus. Four ATCC strains of M. luteus have been tested and three are active on histidine or trans-UCA; two are active on cis-UCA. Micrococci that degrade cis-UCA contain a new enzyme, cis-UCA isomerase, which converts the substrate to the trans-isomer. This enzyme provides access to the classical L-histidine degradation pathway. We hypothesize that an epidermal microflora that degrades L-histidine, trans-UCA, or cis-UCA influences the concentration of urocanic acids on the skin and, thus, affects immune suppression.
Subject(s)
Bacteria, Aerobic/enzymology , Histidine/metabolism , Skin/microbiology , Urocanic Acid/metabolism , cis-trans-Isomerases/metabolism , Adult , Animals , Bacteria, Aerobic/metabolism , Humans , Mice , Mice, Inbred BALB CABSTRACT
Irradiation of skin by sunlight or ultraviolet B (UVB, 290-320 nm) brings about a downregulation of cell-mediated immunity. An action spectrum for photoimmune suppression in mice indicates that trans-urocanic acid absorbs UV photons and is isomerized to the cis-isomer in the stratum corneum. Cis-urocanic acid is subsequently shown to suppress cellular immunity in mice. When histidine is elevated in a mouse diet, a higher level of urocanic acid is detected in mouse skin. These mice are more susceptible to photoimmune suppression. There is evidence that humans and animals experiencing protein malnutrition have very high levels of urocanic acid and/or histidine. Urocanic acid is formed by deamination of histidine in one enzymatic step. We discuss the protein malnutrition of kwashiorkor patients. They experience suppressed immunity and disturbed histidine metabolism. Here, we present a testable hypothesis: one cause of the immune deficiency observed in humans with protein malnutrition is the photoconversion by UVB of increased levels of trans-urocanic acid in skin to cis-urocanic acid, which suppresses the cellular immune system.
