Beschreibung:
<jats:title>Abstract</jats:title><jats:p><jats:italic>Talaromyces marneffei</jats:italic> (TM) immune evasion is an important factor leading to the high mortality rate of Penicilliosis marneffei. <jats:italic>N</jats:italic><jats:sup>6</jats:sup>‐methyladenosine (m<jats:sup>6</jats:sup>A) plays important roles in host immune response to various pathogen infections, yet its role in TM and HIV/TM coinfection remains largely unexplored. Here we reported genome‐wide transcriptional m<jats:sup>6</jats:sup>A profiles of TM mono‐infection and HIV/TM coinfection. Our finding revealed dynamic alterations in global m<jats:sup>6</jats:sup>A levels and upregulation of the m<jats:sup>6</jats:sup>A reader YTH N<jats:sup>6</jats:sup>‐methyladenosine RNA binding protein C2 (YTHDC2) in TM‐infected macrophages. Knockdown of YTHDC2 in TM‐infected cells showed an elevated expression of TLR2 through m<jats:sup>6</jats:sup>A‐dependence, along with upregulation of TNF‐α and IL1‐β. Overall, we characterized the m<jats:sup>6</jats:sup>A profiles of the host and fungus before and after TM infection, and demonstrated that YTHDC2 mediates the key m<jats:sup>6</jats:sup>A site of TLR2 to exert its function. These findings provide new insights into the underlying mechanisms and novel therapeutic approaches for TM diseases.</jats:p>