Work

HIF-α signaling regulates the macrophage inflammatory response during Leishmania major infection 4332

Year: 2025

Type: article

Abstract: Description Cutaneous leishmaniasis (CL) contributes significantly to the global burden of neglected tropical diseases, with 12 million people infected with Leishmania parasites. CL encompasses a range of disease manifestations, from self-healing skin lesions to permanent disfigurations. Macrophage HIF-α-mediated lymphangiogenesis is necessary to achieve efficient wound resolution during murine L. major infection. Here, we investigate the role of macrophage HIF-α signaling independent of lymphangiogenesis. Macrophages from mice with intact HIF-α signaling or mice with deleted HIF-α signaling were subjected to RNASequencing after L. major infection and under pro-inflammatory stimulus. L. major infection alone is sufficient to induce some minor HIF-α-dependent transcriptomic changes, while infection with L. major in combination with pro-inflammatory stimuli induces numerous transcriptomic changes that are both dependent and independent of HIF-a signaling. We found HIF-α suppresses pathways involved in protein translation during L. major infection in a pro-inflammatory environment. Together, these findings show L. major induces a HIF-a-dependent transcriptomic program, but HIF-a only suppresses protein translation in a pro-inflammatory environment. Thus, this work reveals the host inflammatory response, rather than the parasite, largely contributes to myeloid HIF-α signaling during Leishmania infection. Funding Sources NIGMS P20-GM103625, NCATS TL1 TR003109 and UL1 TR003107, NIH T32 GM106999 NIGMS P20-GM121293, and NSF OIA-1946391. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.2030