Macrophage-associated wound healing contributes to African green monkey SIV pathogenesis control

Authors

Fredrik Barrenas, University of Washington & Uppsala University
Kevin Raehtz, University of Pittsburgh
Cuiling Xu, University of Pittsburgh
Lynn Law, University of Washington
Richard R. Green, University of Washington
Guido Silvestri, Emory University
Steven E. Bosinger, Emory University
Andrew Nishida, University of Washington
Qingsheng Li, University of Nebraska-LincolnFollow
Wuxun Lu, University of Nebraska-Lincoln
Jianshui Zhang, University of Nebraska-Lincoln
Matthew J. Thomas, University of Washington
Jean Chang, University of Washington
Elise Smith, University of Washington
Jeffrey M. Weiss, University of Washington
Reem A. Dawoud, Emory University
George H. Richter, University of Pittsburgh
Anita Trichel, University of Pittsburgh
Dongzhu Ma, University of Pittsburgh
Xinxia Peng, North Carolina State University
Jan Komorowski, Uppsala University
Cristian Apetrei, University of Pittsburgh
Ivona Pandrea, University of Pittsburgh
Michael Gale Jr., University of WashingtonFollow

ORCID IDs

http://orcid.org/0000-0003-4101-4073

http://orcid.org/0000-0002-0117-3582

http://orcid.org/0000-0002-0766-8789

http://orcid.org/0000-0002-6332-7436

Date of this Version

11-8-2019

Citation

The Author(s) 2019

Comments

(2019) 10:5101 | https://doi.org/10.1038/s41467-019-12987-9 | www.nature.com/naturecommunications

Abstract

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.