Reprogramming of host energy metabolism mediated by the TNF-iNOS-HIF-1α axis plays a key role in host resistance to<i>Plasmodium</i>infection
Summary TNF has a dual effect inPlasmodiuminfection, bolstering the host’s immune defense while also triggering disease. 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 inP. chabaudi(Pc)-infected mice. We also demonstrate that TNF is required for expression of inducible nitric oxide synthase (iNOS), stabilization of HIF-1α, expression of glucose transporter GLUT1 and enhanced glycolysis in monocytic cells fromPc-infected mice. Importantly,Pc- infected iNOS-/-, TNFRΔLyz2andHIF-1αΔLyz2mice show impaired release of TNF and glycolysis in monocytes, together with increased parasitemia and disease tolerance. Together, our findings reveal that TNF-iNOS-HIF-1α-induced glycolysis in monocytes plays a critical role in host defense and sickness behavior inPc-infected mice..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 01. Apr. Zur Gesamtaufnahme - year:2024 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Matteucci, Kely C. [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.1101/2024.03.26.586751 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI043091180 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI043091180 | ||
| 003 | DE-627 | ||
| 005 | 20240405120338.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240330s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2024.03.26.586751 |2 doi | |
| 035 | |a (DE-627)XBI043091180 | ||
| 035 | |a (biorXiv)10.1101/2024.03.26.586751 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Matteucci, Kely C. |e verfasserin |0 (orcid)0000-0002-2474-1837 |4 aut | |
| 245 | 1 | 0 | |a Reprogramming of host energy metabolism mediated by the TNF-iNOS-HIF-1α axis plays a key role in host resistance to<i>Plasmodium</i>infection |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Summary TNF has a dual effect inPlasmodiuminfection, bolstering the host’s immune defense while also triggering disease. 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 inP. chabaudi(Pc)-infected mice. We also demonstrate that TNF is required for expression of inducible nitric oxide synthase (iNOS), stabilization of HIF-1α, expression of glucose transporter GLUT1 and enhanced glycolysis in monocytic cells fromPc-infected mice. Importantly,Pc- infected iNOS-/-, TNFRΔLyz2andHIF-1αΔLyz2mice show impaired release of TNF and glycolysis in monocytes, together with increased parasitemia and disease tolerance. Together, our findings reveal that TNF-iNOS-HIF-1α-induced glycolysis in monocytes plays a critical role in host defense and sickness behavior inPc-infected mice. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Assis, Patricia A. |e verfasserin |4 aut | |
| 700 | 1 | |a Hirako, Isabella C. |e verfasserin |4 aut | |
| 700 | 1 | |a Leite, Nathalia P. S. |e verfasserin |4 aut | |
| 700 | 1 | |a Pioto, Franciele |e verfasserin |4 aut | |
| 700 | 1 | |a Ojelabi, Ogooluwa |e verfasserin |4 aut | |
| 700 | 1 | |a Toller-Kawahisa, Juliana E. |e verfasserin |4 aut | |
| 700 | 1 | |a Costa, Diego L. |e verfasserin |4 aut | |
| 700 | 1 | |a Da Silva, João S. |e verfasserin |4 aut | |
| 700 | 1 | |a Alves-Filho, José C. |e verfasserin |4 aut | |
| 700 | 1 | |a Gazzinelli, Ricardo T. |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2024) vom: 01. Apr. |
| 773 | 1 | 8 | |g year:2024 |g day:01 |g month:04 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2024.03.26.586751 |m X:VERLAG |x 0 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 01 |c 04 | ||