Details

Autor(en) / Beteiligte

• Hollwedel, Femke D
• Maus, Regina
• Stolper, Jennifer
• Iwai, Satoru
• Kasai, Hayato
• Holtfreter, Silva
• Pich, Andreas
• Neubert, Lavinia
• Welte, Tobias
• Yamasaki, Sho
• Maus, Ulrich A

Titel

Ectopic expression of C-type lectin Mincle renders mice susceptible to staphylococcal pneumonia

Ist Teil von

• The Journal of infectious diseases, 2024-07, Vol.230 (1), p.198-208

Ort / Verlag

United States

Erscheinungsjahr

2024

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Staphylococcus aureus is a prevalent pathogen in pneumonia and harbors glycolipids which may serve as molecular patterns in Mincle (Macrophage inducible C-type lectin) dependent pathogen recognition. We examined the role of Mincle in lung defense against S. aureus in WT, Mincle KO and Mincle transgenic (tg) mice. Two glycolipids, glucosyl-diacylglycerol (Glc-DAG) and diglucosyl-diacylglycerol (Glc2-DAG) were purified, of which only Glc-DAG triggered Mincle reporter cell activation and professional phagocyte responses. Proteomic profiling revealed that Glc2-DAG blocked Glc-DAG-induced cytokine responses, thereby acting as inhibitor of Glc-DAG/Mincle-signaling. WT mice responded to S. aureus with a similar lung pathology as Mincle KO mice, most likely due to Glc2-DAG-dependent inhibition of Glc-DAG/Mincle-signaling. In contrast, ectopic Mincle expression caused severe lung pathology in S. aureus-infected mice characterized by bacterial outgrowth and fatal pneumonia. Collectively, Glc2-DAG inhibits Glc-DAG/Mincle-dependent responses in WT mice, whereas sustained Mincle expression overrides Glc2-DAG-mediated inhibitory effects, conferring increased host susceptibility to S. aureus.