Mycobacterium tuberculosis Infection of Retinal Endothelial Cells Induces Interferon Signaling Activation: Insights...

Ocular tuberculosis (OTB) has diverse clinical presentations, among which choroidal granuloma and tubercular retinal vasculitis (TRV) are recognized as typical phenotypes. The potential role of human retinal endothelial cells (RECs) in regulating inflammation in response to Mycobacterium tuberculosis (Mtb) infection, particularly relevant in cases of TRV, remains elusive. This study investigated the cellular defense of Mtb-exposed RECs.

Human RECs, as a TRV model, were exposed to either live H37Rv Mtb or heat-killed (HK)-H37Rv Mtb. Total RNA and culture supernatants were collected 24 hours post-exposure, and cellular responses were characterized using RNA sequencing and bioinformatics analysis.

Both live and HK-Mtb were internalized by RECs, but only live Mtb induced a robust transcriptional response, with 322 differentially expressed genes. Live Mtb infection, but not HK-Mtb exposure, induced a dominant interferon (IFN) signaling response, particularly type I IFN activation. This was validated by real-time polymerase chain reaction (RT-PCR) for 10 IFN-inducible genes. Network analysis suggested a role of RECs in leucocyte recruitment and activation. Although HK-Mtb increased the production of CCL2, IL-6, and IL-8, this was not observed with live Mtb infection. Instead, live Mtb infection led to elevated CXCL10 and IP-10 production.

RECs elicit a robust immune response to Mtb infection. IFN signaling activation was observed in live Mtb-infected RECs but not in HK-Mtb-exposed RECs. These findings provide insights into TRV pathogenesis and offer clues for potential biomarkers that may help differentiate TRV caused by active infection, which requires antitubercular treatment, from cases without active infection, which require immunosuppressive therapy alone.