Work

Intervening in the lung microbiome mitigates herpesvirus-triggered post-HCT pulmonary fibrosis by enhancing PD-L1 expression on dendritic cells 3532

Year: 2025

Type: article

Abstract: Description Alterations to the lung microbiome are frequently associated with adverse pulmonary pathologies. Hematopoietic stem cell transplantation (HCT) disrupts the lung microbiome and increases the risk of post-transplant lung fibrosis. In a mouse model of post-HCT pulmonary fibrosis following infection with murine gammaherpesvirus 68 (MHV-68), we observed a reduction in Lactobacillus johnsonii in the lung microbiome. Administering live or heat-killed (HK) L. johnsonii intranasally to MHV-68-infected HCT mice significantly reduced lung fibrosis. Notably, HK L. johnsonii decreased Il17a expression in CD4 T cells without affecting Th17 cell numbers, which is associated with increased PD-L1 expression in lung dendritic cells. This suggests the involvement of the PD-L1/PD-1 pathway in suppressing Th17 cell activity. Bone marrow-derived dendritic cells (BMDCs) increased their cell surface PD-L1 after treatment with HK L. johnsonii, leading to suppressed IL-17 production in induced Th17 cells. Furthermore, the effects of HK L. johnsonii in reducing lung fibrosis were diminished in PD-1-deficient HCT mice. Our findings strongly suggest that HK L. johnsonii lessens herpesvirus-mediated pulmonary fibrosis by inhibiting IL-17A production via PD-L1/PD-1 signaling, presenting a promising postbiotic therapeutic approach to modulate immune responses in post-HCT pulmonary complications. Funding Sources Supported by NIH R01HL153028, R35HL144481, R01HL162659, R01AI138348, R21AI163720, the Nina and Jerry D. Luptak Endowment of the MHWFAC. Topic Categories Mucosal and Regional Immunology (MUC)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1325