The Role of Talaromyces Marneffei Binding To CD86 in the CD86-CTLA4 Regulatory Pathway.

Talaromyces marneffei (TM), an opportunistic pathogenic fungus, binds to CD86, which acts as a co-stimulatory molecule for CTLA4. CD86 activates CTLA4, which transmits inhibitory signals, yet its role in TM immune responses remains unclear. In this study, we investigated how the binding of TM to CD86 modulates the CD86-CTLA4 regulatory pathway. To establish the co-culture system of THP-1/THP-1-CD86-EGFP, TM, and Jurkat, Jurkat cells were first transfected with lentivirus to generate the target cell lines. The interactions among TM, CD86, and CTLA4 within this system were then investigated using confocal fluorescence microscopy. To evaluate changes in the expression levels of target factors, RT-qPCR and Western blotting were performed. Potential downregulated pathways were further identified through RNA sequencing (RNA-Seq) analysis. Additionally, the functional role of CTLA4 in the co-culture system was assessed by bactericidal assays. In the co-culture system, THP-1 macrophages engulfed TM, which bound to CD86 and formed immature phagosomes that subsequently escaped. Escaped TM interacted with Jurkat cells via CD86, activating CTLA4. Transcriptional levels of CD86 and CTLA4 initially increased and then decreased in the TM(+) vs. TM(-) comparison. After 24 h, OE showed significant differences in CD86 and CTLA4 (transcriptional and translational levels) vs. CON and NC, along with differences in IFN-γ, IL-5, and IL-13. At 48 h, CD86 and CTLA4 expression varied with THP-1/CD86-EGFP presence. RNA-seq showed TM proliferation and differentiation downregulated PI3K-Akt and T cell receptor pathways. The fungal killing assay indicated that CTLA4 may facilitate TM in evading immune-mediated damage. TM regulates the CD86-CTLA4 immune regulatory pathway by binding to the CD86 protein, thereby evading the immune killing of macrophages.