Langhans giant cells regulate cutaneous immune responses during mycobacterial infection through CXCL1/CXCL2 secretion

Mycobacterial infection poses a significant threat to human health, with granuloma formation serving as a hallmark pathological feature and a critical diagnostic indicator. Langhans giant cells (LGCs) play a pivotal role in the immune response during mycobacterial infections, yet their immunological functions remain incompletely understood. In this study, we explored the role of LGCs in immune modulation during mycobacterial infection. RNA sequencing analysis revealed that mycobacterial infection significantly upregulated the expression of chemokines CXCL1 and CXCL2 in LGCs. These chemokines promoted macrophage migration and enhanced the secretion of pro-inflammatory cytokines, such as IL-1β and IFN-γ, via CXCR2 receptor interaction. Furthermore, CXCL1 and CXCL2 facilitated macrophage fusion, contributing to granuloma formation. We also demonstrated that mycobacterial infection activated TLR2 on LGCs, leading to the upregulation of CXCL1 and CXCL2. Additionally, inhibition of the NF-κB pathway resulted in decreased chemokine secretion, confirming its role in regulating LGC-mediated immune responses. These findings highlight the critical role of CXCL1 and CXCL2 in the immunological functions of LGCs, highlighting their importance in amplifying immune responses and driving granuloma formation during mycobacterial infection.