RESUMO
IL-17 plays important roles in host defense against Candida albicans at barrier surfaces and during invasive infection. However, the role of IL-17 in host defense after colonization of the epidermis, a main site of C. albicans infection, remains poorly understood. Using a murine model of epicutaneous candidiasis without skin abrasion, we found that skin inflammation triggered by epidermal C. albicans colonization was self-limiting with fungal clearance completed by day 7 after inoculation in wild-type mice or animals deficient in IL-17A or IL-17F. In contrast, marked neutrophilic inflammation in the epidermis and impaired fungal clearance were observed in mice lacking both IL-17A and IL-17F. Clearance of C. albicans was independent of Dectin-1, Dectin-2, CARD9 (caspase-recruitment domain family, member 9), TLR2 (Toll-like receptor 2) and MyD88 in the epidermal colonization model. We found that group 3 innate lymphoid cells (ILC3s) and γδT cells were the major IL-17 producers in the epicutaneous candidiasis model. Analyses of Rag2-/- mice and Rag2-/-Il2rg-/- mice revealed that production of IL-17A and IL-17F by ILC3s was sufficient for C. albicans clearance. Finally, we found that depletion of neutrophils impaired C. albicans clearance in the epidermal colonization model. Taken together, these findings indicate a critical and redundant function of IL-17A and IL-17F produced by ILC3s in host defense against C. albicans in the epidermis. The results also suggest that epidermal C. albicans clearance is independent of innate immune receptors or that these receptors act redundantly in fungal recognition and clearance.
Assuntos
Candida albicans , Candidíase , Interleucina-17/imunologia , Animais , Proteínas Adaptadoras de Sinalização CARD , Epiderme/metabolismo , Imunidade Inata , Inflamação , Linfócitos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
A three-year-old Sri Lankan boy residing in Japan developed a nodule on his scalp after visiting Sri Lanka. Two months later, the lesion increased in size to 22 × 19 mm(2), and was identified as an erythematous nodule with alopecia. Direct examination of the infected hair shafts indicated fungal hyphae outside the shafts. The fungus was identified as Microsporum gypseum following mycological examination. The sequence of the internal transcribed spacer 1 region of ribosomal RNA gene (ITS1 rDNA) exhibited 95.7-100.0% homology with that of Arthroderma incurvatum. The patient was successfully treated with a 6-week itraconazole course. We also examined DNA samples from eight clinical isolates of A. incurvatum. Alignments of ITS1 sequences of these strains and our isolate, showed gaps in the 64-bp positions 140-142 and 141-143 of the 205-207-bp ITS1 alignment. We performed phylogenetic analysis using the neighbor-jointing (NJ) method based on the ITS1 sequences of the present isolate and twenty related strains. Fifteen A. incurvatum strains were divided into East Asia and non-East Asia clusters. The present isolate belonged to the non-East Asia cluster, suggesting that the patient was infected outside Japan. Moreover, the trees suggested area-dependent genetic polymorphism of A. incurvatum.
Assuntos
Arthrodermataceae/isolamento & purificação , Filogeografia , Polimorfismo Genético , Tinha do Couro Cabeludo/diagnóstico , Tinha do Couro Cabeludo/microbiologia , Antifúngicos/administração & dosagem , Sequência de Bases , Pré-Escolar , Análise por Conglomerados , DNA Fúngico/química , DNA Fúngico/genética , DNA Ribossômico/química , DNA Ribossômico/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Humanos , Itraconazol/administração & dosagem , Japão , Masculino , Microscopia , Dados de Sequência Molecular , Couro Cabeludo/patologia , Alinhamento de Sequência , Análise de Sequência de DNA , Sri Lanka , Resultado do TratamentoAssuntos
Hipertermia Induzida , Infecções por Mycobacterium não Tuberculosas/terapia , Mycobacterium chelonae/crescimento & desenvolvimento , Dermatopatias Bacterianas/terapia , Idoso , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Humanos , Masculino , Minociclina/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/patologia , Mycobacterium chelonae/efeitos dos fármacos , Mycobacterium chelonae/isolamento & purificação , Infiltração de Neutrófilos , Ofloxacino/uso terapêutico , Prednisolona/uso terapêutico , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/patologia , Resultado do TratamentoRESUMO
We report a lymphocutaneous type of nocardiosis caused by Nocardia vinacea. A 62-year-old woman with polymyositis presented with some erythematous swellings and subcutaneous abscesses on her right middle finger and the dorsum of her hand, which had persisted for 2 weeks. Culturing of the excised nodule and pus revealed orange to orange-tan colonies with scanty whitish aerial mycelia. The isolate was identified as N. vinacea on the basis of its biochemical and chemotaxonomic characteristics and the results of molecular biological analysis. In our case, oral minocycline (MINO) and trimethoprim-sulfamethoxazole (TMP-SMX) for 7 weeks did not improve the clinical manifestation, even though in vitro susceptibility testing of the isolate predicted its susceptibility to MINO and TMP-SMX. Treatment with partial surgical excision followed by TMP-SMX and meropenem administration was effective. This is the first reported case of a lymphocutaneous type of nocardiosis caused by N. vinacea.
