bromochloroacetic-acid and Opportunistic-Infections

Dermatophytosis is a skin infection caused by keratinophilic, filamentous fungi. These are highly prevalent, common mycoses, affecting approximately 20% of the population. These fungi invade the stratum corneum, and other keratinised tissues, like nails and hair, where they grow by secreting enzymes and degrading keratin to obtain nutrients. Clinical presentation is variable and may depend on many factors, such as the infection site, the host's immunity and the dermatophyte's virulence. Generally, patients with acute superficial dermatophytosis mount cell-mediated immune responses. However, those suffering from chronic or recurrent infections are unable to develop this response, for reasons yet unknown. Several reports have described severe and occasionally life-threatening invasive diseases (deep dermatophytosis) associated with genetic mutations in the innate immunity-associated molecule CARD9, displaying the need to better understand its immune response. These dermatoses have substantial clinical consequences, producing chronic and difficult to treat skin lesions. They also lead to a decline in the patient's quality of life and impact their self-esteem. This review summarises findings on the immune response against dermatophytes.

Topics: Adaptive Immunity; CARD Signaling Adaptor Proteins; Dermatomycoses; Hair; Humans; Immunity; Immunity, Cellular; Immunity, Innate; Keratins; Nails; Opportunistic Infections; Skin; Trichophyton

The hormonal form of vitamin D(3), 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), is an immune system modulator and induces expression of the TLR coreceptor CD14. 1,25(OH)(2)D(3) signals through the vitamin D receptor, a ligand-stimulated transcription factor that recognizes specific DNA sequences called vitamin D response elements. In this study, we show that 1,25(OH)(2)D(3) is a direct regulator of antimicrobial innate immune responses. The promoters of the human cathelicidin antimicrobial peptide (camp) and defensin beta2 (defB2) genes contain consensus vitamin D response elements that mediate 1,25(OH)(2)D(3)-dependent gene expression. 1,25(OH)(2)D(3) induces antimicrobial peptide gene expression in isolated human keratinocytes, monocytes and neutrophils, and human cell lines, and 1,25(OH)(2)D(3) along with LPS synergistically induce camp expression in neutrophils. Moreover, 1,25(OH)(2)D(3) induces corresponding increases in antimicrobial proteins and secretion of antimicrobial activity against pathogens including Pseudomonas aeruginosa. 1,25(OH)(2)D(3) thus directly regulates antimicrobial peptide gene expression, revealing the potential of its analogues in treatment of opportunistic infections.

Topics: Adjuvants, Immunologic; Antimicrobial Cationic Peptides; beta-Defensins; Calcitriol; Cathelicidins; Cell Line; Gene Expression Regulation; Humans; Immunity, Innate; Keratinocytes; Keratins; Monocytes; Neutrophils; Opportunistic Infections; Pseudomonas Infections; Receptors, Calcitriol; Vitamin D Response Element