CD4 T cell contact drives macrophage cell cycle progression and susceptibility to lentiviral transduction
Abstract Macrophages are typically quiescent cells residing in G0, though tissue macrophages have been shown to proliferate locally in tissues; we previously demonstrated that differentiated monocyte derived macrophages (MDM) can be stimulated to re-enter G1 phase of the cell cycle from G0, without cell division. Entry into G1 correlates with an increase in CDK1 expression which phosphorylates the deoxynucleotide-triphosphate hydrolase SAMHD1 at position 592. SAMHD1 not only regulates cellular dNTP levels, but is also a restriction factor for virus replication of HIV-1 and DNA viruses. Here we show that contact with autologous CD4 T cells leads to antigen-independent macrophage cell cycle progression from G0-G1, accompanied by expression of cell cycle associated proteins, including CDK1, and the activation of the canonical MEK-ERK pathway. Further, macrophage cell cycle progression can be blocked not only by anti-cancer drugs targeting the MEK-ERK axis such as Palcociclib, but also by pre-treatment with EGFR antibody, providing additional evidence for cell surface interactions driving proliferative responses. Cell contact with uninfected CD4 T cells renders macrophages ten-fold more susceptible to transduction with VSV-G pseudotyped HIV-1 particles..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 19. Jan. Zur Gesamtaufnahme - year:2024 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Mlcochova, Petra [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.1101/2024.01.15.575666 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI042179033 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI042179033 | ||
| 003 | DE-627 | ||
| 005 | 20240120090251.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240117s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2024.01.15.575666 |2 doi | |
| 035 | |a (DE-627)XBI042179033 | ||
| 035 | |a (biorXiv)10.1101/2024.01.15.575666 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Mlcochova, Petra |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a CD4 T cell contact drives macrophage cell cycle progression and susceptibility to lentiviral transduction |
| 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 Abstract Macrophages are typically quiescent cells residing in G0, though tissue macrophages have been shown to proliferate locally in tissues; we previously demonstrated that differentiated monocyte derived macrophages (MDM) can be stimulated to re-enter G1 phase of the cell cycle from G0, without cell division. Entry into G1 correlates with an increase in CDK1 expression which phosphorylates the deoxynucleotide-triphosphate hydrolase SAMHD1 at position 592. SAMHD1 not only regulates cellular dNTP levels, but is also a restriction factor for virus replication of HIV-1 and DNA viruses. Here we show that contact with autologous CD4 T cells leads to antigen-independent macrophage cell cycle progression from G0-G1, accompanied by expression of cell cycle associated proteins, including CDK1, and the activation of the canonical MEK-ERK pathway. Further, macrophage cell cycle progression can be blocked not only by anti-cancer drugs targeting the MEK-ERK axis such as Palcociclib, but also by pre-treatment with EGFR antibody, providing additional evidence for cell surface interactions driving proliferative responses. Cell contact with uninfected CD4 T cells renders macrophages ten-fold more susceptible to transduction with VSV-G pseudotyped HIV-1 particles. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Heilig, Raphael |4 aut | |
| 700 | 1 | |a Fischer, Roman |0 (orcid)0000-0002-9715-5951 |4 aut | |
| 700 | 1 | |a Gupta, Ravindra K. |0 (orcid)0000-0001-9751-1808 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2024) vom: 19. Jan. |
| 773 | 1 | 8 | |g year:2024 |g day:19 |g month:01 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2024.01.15.575666 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 19 |c 01 | ||