AUTHOR=Jiao Qingqing , Luo Ying , Scheffel Jörg , Geng Peng , Wang Yuhan , Frischbutter Stefan , Li Ruoyu , Maurer Marcus , Zhao Zuotao 

TITLE=Skin Mast Cells Contribute to Sporothrix schenckii Infection

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00469

DOI=10.3389/fimmu.2020.00469

ISSN=1664-3224

ABSTRACT=<p><bold>Background:</bold><italic>Sporothrix schenckii</italic> (<italic>S. schenckii</italic>), a dimorphic fungus, causes sporotrichosis. Mast cells (MCs) have been described to be involved in skin fungal infections. The role of MCs in cutaneous sporotrichosis remains largely unknown.</p><p><bold>Objectives:</bold> To characterize the role and relevance of MCs in cutaneous sporotrichosis.</p><p><bold>Methods:</bold> We analyzed cutaneous sporotrichosis in wild-type (WT) mice and two different MC-deficient strains. <italic>In vitro</italic>, MCs were assessed for <italic>S. schenckii</italic>-induced cytokine production and degranulation after incubation with <italic>S. schenckii</italic>. We also explored the role of MCs in human cutaneous sporotrichosis.</p><p><bold>Results:</bold> WT mice developed markedly larger skin lesions than MC-deficient mice (&gt; 1.5 fold) after infection with <italic>S. schenckii</italic>, with significantly increased fungal burden. <italic>S. schenckii</italic> induced the release of tumor necrosis factor alpha (TNF), interleukin (IL)-6, IL-10, and IL-1β by MCs, but not degranulation. <italic>S. schenckii</italic> induced larger skin lesions and higher release of IL-6 and TNF by MCs as compared to the less virulent <italic>S. albicans</italic>. In patients with sporotrichosis, TNF and IL-6 were increased in skin lesions, and markedly elevated levels in the serum were linked to disease activity.</p><p><bold>Conclusions:</bold> These findings suggest that cutaneous MCs contribute to skin sporotrichosis by releasing cytokines such as TNF and IL-6.</p>