13:40 - 15:10
Room: ANA Crowne Plaza “Ohtori” Room A
Workshop Session
Chair/s:
Mitsutoshi Yoneyama, Shinobu Saijo
Pathogenic fungus, Trichophyton mentagrophytes negatively regulates host immune responses via Siglec receptors.
Yasunobu Miyake1, Eri Suematsu1, Shinobu Saijo2, Sho Yamasaki2, 3, 4, Hiroki Yoshida1
1Saga University, Faculty of Medicine, Saga, Japan, 2Chiba University, Medical Mycology Research Center, Chiba, Japan, 3Osaka University, Research Institute for Microbial Diseases, Osaka, Japan, 4Kyushu University, Medical Institute of Bioregulation, Fukuoka, Japan

Innate immune cells such as macrophages and dendritic cells sense invading pathogens through pattern recognition receptors (PRRs), and control host immune responses. Among these PRRs, Siglec is a sialic acid-binding lectin and negatively regulates host immune responses through cytoplasmic ITIM sequence. To find Siglec-binding pathogens, we generated Siglec reporter cells that can detect ligand recognition by GFP expression, and found Trichophyton mentagrophytes. Trichophyton mentagrophytes is a pathogenic fungus that causes dermatomycosis. Although immunocompromised patients often suffer from dermatomycosis, Trichophyton mentagrophytes also infects healthy individuals and causes ringworm and athlete’s foot. Taken together, we speculated that Trichophyton mentagrophytes escapes from host immunity through the interaction with Siglec receptor. Trichophyton mentagrophytes potently bound to Siglec-5 and Siglec-9, and moderately interacted with Siglec-3, all of which are expressed on macrophages and monocytes. Upon ligation of Siglec with Trichophyton mentagrophytes in human monocytic U937 cells, SHP-1 but not SHP-2 was recruited to ITIM sequence in the cytoplasmic region, resulting in inhibition of immune responses including the production of TNFα. Sialidase treatment of Trichophyton mentagrophytes had no impact on the recognition of Siglecs, suggesting that the ligand is not a sialic acid. We are now investigating the nature of this unique ligand. In conclusion, Trichophyton mentagrophytes negatively regulates host immune responses through immunosuppressive receptor, Siglec. This interaction should be a potential target for new anti-fungal drugs.


Reference:
Mo-WS1-2
Session:
Workshop 1, ‟Innate immunity and infection”
Presenter/s:
Yasunobu Miyake
Presentation type:
Oral Presentation
Room:
ANA Crowne Plaza “Ohtori” Room A
Chair/s:
Mitsutoshi Yoneyama, Shinobu Saijo
Date:
Monday, 30 October 2017
Time:
13:50 - 14:00
Session times:
13:40 - 15:10