title: Fast disease progression in simian HIV-infected female macaque is accompanied by a robust local inflammatory innate immune and microbial response.
abstract: OBJECTIVE
  Gender differences in immune response and the rate of disease progression in HIV-infected individuals have been reported but the underlying mechanism remains unclear, in part because of the lack of relevant animal models. Here, we report a novel nonhuman primate model for investigation of sex disparity in HIV disease progression.
  
  
  METHODS
  Viral load and rate of disease progression were evaluated in rhesus macaques infected intrarectally with lineage-related subtype C R5 simian HIVs. Cytokine/chemokine levels in rectal swab eluates, and bacterial species adherent to the swabs and in the feces were determined.
  
  
  RESULTS
  Simian HIV-infected female rhesus macaques progressed faster to AIDS than male macaques, recapitulating the sex bias in HIV-1 disease in humans. There were no significant differences in the levels of soluble immune mediators in the rectal mucosa of naive female and male macaques. However, an exploratory longitudinal study in six infected macaques indicates that the female macaques mounted an earlier and more robust proinflammatory skewed rectal immune response to infection. Moreover, expansion of Proteobacteria that increase in other intestinal inflammatory disorders was significantly higher in the rectal mucosa of female than male macaques during acute infection.
  
  
  CONCLUSIONS
  These findings suggest that sex differences in local innate immune activation and compositional shifts in the gut microbiota could be the drivers of increased disease susceptibility in female macaques. Further studies with this novel nonhuman primate model of HIV infection could lead to innovative research on gender differences, which may have important therapeutic implications for controlling disease in infected men as well as women.
authors.affiliation: aAaron Diamond AIDS Research Center, The Rockefeller University bDepartment of Pathology and Medicine, New York University School of Medicine, New York, New York cPublic Health Research Institute, Rutgers, the State University of New Jersey, New Jersey Medical School, Newark, New Jersey dTulane National Primate Research Center, Tulane University Medical Center, Covington, Louisiana eDepartment of Preventive Medicine and Community Health, Rutgers, the State University of New Jersey, New Jersey Medical School, Newark, New Jersey fDepartment of Veterans Affairs New York Harbour Healthcare System, New York, New York, USA.
authors.forename: Wuze
authors.initials: W
authors.lastname: Ren
authors.forename: Yingfei
authors.initials: Y
authors.lastname: Ma
authors.forename: Liying
authors.initials: L
authors.lastname: Yang
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.forename: January
authors.initials: J
authors.lastname: Salas
authors.forename: Kasi
authors.initials: K
authors.lastname: Russell
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.forename: Amy
authors.initials: A
authors.lastname: Davidow
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Pei
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Chang
authors.forename: Cecilia
authors.initials: C
authors.lastname: Cheng-Mayer
mesh_terms: D000818:Animals; D058448:Biota; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D018450:Disease Progression; D004198:Disease Susceptibility; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology* / Q000473:pathology*; D008253:Macaca mulatta; D008297:Male; D012007:Rectum / Q000382:microbiology / Q000473:pathology; D012737:Sex Factors; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D019562:Viral Load
chemical_list: D016207:Cytokines