Macrophage-associated wound healing contributes to African green monkey SIV pathogenesis control.
Fredrik BarrenasKevin RaehtzCuiling XuLynn LawRichard R GreenGuido SilvestriSteven E BosingerAndrew NishidaQingsheng LiWuxun LuJianshui ZhangMatthew J ThomasJean ChangElise SmithJeffrey M WeissReem A DawoudGeorge H RichterAnita TrichelDongzhu MaXinxia PengJan KomorowskiCristian ApetreiIvona PandreaMichael GalePublished in: Nature communications (2019)
Natural hosts of simian immunodeficiency virus (SIV) avoid AIDS despite lifelong infection. Here, we examined how this outcome is achieved by comparing a natural SIV host, African green monkey (AGM) to an AIDS susceptible species, rhesus macaque (RM). To asses gene expression profiles from acutely SIV infected AGMs and RMs, we developed a systems biology approach termed Conserved Gene Signature Analysis (CGSA), which compared RNA sequencing data from rectal AGM and RM tissues to various other species. We found that AGMs rapidly activate, and then maintain, evolutionarily conserved regenerative wound healing mechanisms in mucosal tissue. The wound healing protein fibronectin shows distinct tissue distribution and abundance kinetics in AGMs. Furthermore, AGM monocytes exhibit an embryonic development and repair/regeneration signature featuring TGF-β and concomitant reduced expression of inflammatory genes compared to RMs. This regenerative wound healing process likely preserves mucosal integrity and prevents inflammatory insults that underlie immune exhaustion in RMs.
Keyphrases
- wound healing
- stem cells
- genome wide
- genome wide identification
- mesenchymal stem cells
- transcription factor
- cell therapy
- copy number
- oxidative stress
- poor prognosis
- gene expression
- ulcerative colitis
- binding protein
- tissue engineering
- dna methylation
- bone marrow
- long non coding rna
- genome wide analysis
- mouse model
- dendritic cells
- big data
- small molecule