Reprogramming of host energy metabolism mediated by the TNF-iNOS-HIF-1alpha axis plays a key role in host resistance to Plasmodium infection
Matteucci, K. C.; Assis, P. A.; Hirako, I. C.; Leite, N. P. S.; Pioto, F.; OJELABI, O.; E. TOLLER-KAWAHISA, J.; Costa, D. L.; S. Silva, J.; Alves-Filho, J. C.; Gazzinelli, R.
Show abstract
TNF has a dual effect in Plasmodium infection, bolstering the hosts immune defense while also inducing sickness behavior. Here, we show that TNF signaling hampers physical activity, food intake, and energy expenditure while enhancing glucose uptake by the liver and spleen as well as controlling parasitemia in P. chabaudi (Pc)-infected mice. We also report that TNF is required for expression of inducible nitric oxide synthase (iNOS), stabilization of HIF-1, expression of glucose transporter GLUT1 and enhanced glycolysis in monocytic cells from Pc-infected mice. Importantly, Pc-infected iNOS-/-, TNFR{Delta}Lyz2 and HIF-1{Delta}Lyz2 mice show impaired release of TNF and glycolysis in monocytes, along with increased parasitemia and disease tolerance. Altogether, our results indicate that TNF-iNOS-HIF-1-induced glycolysis in monocytes plays a critical role in host defense and sickness behavior in Pc-infected mice. TeaseThe role of host energy metabolism and glycolysis in monocytes as determinant of host resistance to Plasmodium infection and tolerance to disease.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Toxoplasma GRA15 and GRA24 are important activators of the host innate immune response in the absence of TLR11 96%
- Naïve CD8 T cell IFNγ responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma gondii ROP5 95%
- Parasite-Induced IFN-g Regulates Host Defense via CD115 and mTOR-Dependent Mechanism of Tissue-Resident Macrophage Death 95%
Similar papers in this journal
- IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii 95%
- Over-expression Screen of Interferon-Stimulated Genes Identifies RARRES3 as a Restrictor of Toxoplasma gondii Infection 95%
- Plasmodium infection disrupts the T follicular helper cell response to heterologous immunization 95%
Similar papers in this journal
- Toxoplasma gondii GRA28 is required for placenta-specific induction of the regulatory chemokine CCL22 in human and mouse. 95%
- TgIF2K-B is an eIF2α kinase in Toxoplasma gondii that responds to oxidative stress and optimizes pathogenicity 95%
- RNA-Seq Analysis Illuminates the Early Stages of Plasmodium Liver Infection 95%
Similar papers in this journal
- Blockade of LAG-3 in PD-L1-deficient mice enhances clearance of blood stage malaria independent of humoral responses 96%
- Interferon-γ-producing CD4+ T cells drive monocyte activation in the bone marrow during experimental Leishmania donovani infection. 95%
- P2RX7 signaling drives the differentiation of Th1 cells through metabolic reprogramming for aerobic glycolysis 95%
Similar papers in this journal
- Effects of Low-level Persistent Infection on maintenance of immunity by CD4 T cell subsets and Th1 cytokines 95%
- Mucins shed from the laminated layer in cystic echinococcosis are captured by Kupffer cells via the lectin receptor Clec4F 95%
- Elevated levels of interleukin-27 in early life compromise protective immunity during neonatal sepsis 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.