Deciphering HTLV-1-associated Lung Pathology: Inflammation, Monocyte Recruitment and Differentiation Triggered by HTLV-1-exposed Alveolar Epithelial Cells

Individuals with Human T-Lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis are prone to pulmonary complications (e.g., bronchiectasis), linked to chronic inflammation. This study assessed the impact of HTLV-1 infection on lung inflammation by analyzing the alveolar transcriptome of A549 epithelial cells following exposure to HTLV-1. Co-culture with HTLV-1-infected MT-2 cells caused transcriptomic changes related to viral response, NF-kB activation, and inflammation. RT-qPCR confirmed elevated expression of the chemokine monocyte chemotactic protein-1 (MCP-1/CCL2) and CSF-1 in A549 MT-2 co-cultures. Increased CSF-1 expression was mechanistically linked to NF-kB signaling, using CRISPR/Cas9 RELA knockout. Supernatant from A549 MT-2 co-cultures triggered chemotaxis and macrophage differentiation of THP-1 and primary monocytes. STRING analysis revealed enrichment in pathways associated with monocyte infiltration and bronchiectasis, aligning with clinical and multi-ancestry GWAS data. Overall, this study highlights HTLV-1's role in driving inflammation and monocyte recruitment in the alveolar epithelium, potentially contributing to viral persistence and immune evasion.