Natural killer cells are pivotal for in vivo protection following systemic infection by Sporothrix schenckii

Autor(es)

Ferreira, Lucas Souza ^[1] ; Portuondo, Deivys Leandro ^[1] ; Polesi, Marisa Campos ^[1] ; Carlos, Iracilda Zeppone ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ FCF UNESP, Dept Clin Anal, Fac Pharmaceut Sci Araraquara, Araraquara - Brazil

• Tipo de documento: Artigo Científico
• Fonte: IMMUNOLOGY; v. 155, n. 4, p. 467-476, DEC 2018.
• Citações Web of Science: 1

Resumo

Natural killer (NK) cells are one of the first cell types to enter inflammation sites and have been historically known as key effector cells against tumours and viruses; now, accumulating evidence shows that NK cells are also capable of direct in vitro activity and play a protective role against clinically important fungi in vivo. However, our understanding of NK cell development, maturation and activation in the setting of fungal infections is preliminary at best. Sporotrichosis is an emerging worldwide-distributed subcutaneous mycosis endemic in many countries, affecting humans and other animals and caused by various related thermodimorphic Sporothrix species, whose prototypical member is Sporothrix schenckii. We show that following systemic infection of BALB/c mice with S. schenckii sensu stricto, NK cells displayed a more mature phenotype as early as 5 days post-infection as judged by CD11b/CD27 expression. At 10 days post-infection, NK cells had increased expression of CD62 ligand (CD62L) and killer cell lectin-like receptor subfamily G member 1 (KLRG1), but not of CD25 or CD69. Depletion of NK cells with anti-asialo GM1 drastically impaired fungal clearance, leading to a more than eightfold increase in splenic fungal load accompanied by heightened systemic inflammation, as shown by augmented production of the pro-inflammatory cytokines tumour necrosis factor-alpha, interferon-gamma and interleukin-6, but not interleukin-17A, in the spleen and serum. Our study is, to the best of our knowledge, the first to demonstrate that a fungal infection can drive NK cell maturation in vivo and that such cells are pivotal for in vivo protection against S. schenckii. (AU)

• Processo FAPESP: 15/04023-0 - Avaliação de células dendríticas isogênicas ativadas e imiquimode como alternativas terapêuticas na esporotricose em animais imunossuprimidos e imunocompetentes
• Beneficiário: Iracilda Zeppone Carlos
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/04021-8 - Avaliação do papel das células natural killer na infecção por Sporothrix schenckii
• Beneficiário: Lucas Souza Ferreira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado