Spatial and Single-Cell Transcriptomics Identifies SIRPA⁺ Myeloid Cells and CXCR4⁺ Tregs Crosstalk as a Key Regulator of Granuloma-TLS Immune Homeostasis
Description
Pulmonary tuberculosis (PTB) is characterized by granulomas encircled by tertiary lymphoid structures (TLS) that coordinate local immune responses. However, how the crosstalk between granulomas and TLS shapes the host–pathogen balance—specifically, the delicate equilibrium between immune control and immunopathology—remains poorly understood. Our central hypothesis is that Mycobacterium tuberculosis (MTB) exploits myeloid–Treg crosstalk to remodel the local immune microenvironment, thereby promoting its persistence and driving pathogenesis. Specifically, we proposed that SIRPA⁺ myeloid cells negatively regulate TLS maturation through a CXCL12–CXCR4‑dependent mechanism, and that this interaction defines a previously unrecognised dimension of MTB virulence.
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Institutions
- Australian National UniversityAustralian Capital Territory, Canberra