Fast disease progression in simian HIV-infected female macaque is accompanied by a robust local inflammatory innate immune and microbial response

Wuze Ren, Yingfei Ma, Liying Yang, Agegnehu Gettie, January Salas, Kasi Russell, James Blanchard, Amy Davidow, Zhiheng Pei, Theresa L. Chang, Cecilia Cheng-Mayer

Research output: Contribution to journalArticle

10 Citations (Scopus)

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. Design/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 infectedmacaques indicates that the femalemacaquesmountedanearlier andmore 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)F1-F8
JournalAIDS
Volume29
Issue number10
DOIs
StatePublished - Jun 19 2015

Fingerprint

Macaca
Innate Immunity
Disease Progression
HIV
Macaca mulatta
Primates
Mucous Membrane
Sexism
Proteobacteria
Disease Susceptibility
Infection
Viral Load
Chemokines
Feces
Sex Characteristics
HIV Infections
Longitudinal Studies
HIV-1
Acquired Immunodeficiency Syndrome
Animal Models

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Keywords

  • Gut microbiome response
  • Regional innate immunity
  • Sex disparity
  • Simian HIV pathogenesis

Cite this

Ren, Wuze ; Ma, Yingfei ; Yang, Liying ; Gettie, Agegnehu ; Salas, January ; Russell, Kasi ; Blanchard, James ; Davidow, Amy ; Pei, Zhiheng ; Chang, Theresa L. ; Cheng-Mayer, Cecilia. / Fast disease progression in simian HIV-infected female macaque is accompanied by a robust local inflammatory innate immune and microbial response. In: AIDS. 2015 ; Vol. 29, No. 10. pp. F1-F8.
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Fast disease progression in simian HIV-infected female macaque is accompanied by a robust local inflammatory innate immune and microbial response. / Ren, Wuze; Ma, Yingfei; Yang, Liying; Gettie, Agegnehu; Salas, January; Russell, Kasi; Blanchard, James; Davidow, Amy; Pei, Zhiheng; Chang, Theresa L.; Cheng-Mayer, Cecilia.

In: AIDS, Vol. 29, No. 10, 19.06.2015, p. F1-F8.

Research output: Contribution to journalArticle

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AU - Ren, Wuze

AU - Ma, Yingfei

AU - Yang, Liying

AU - Gettie, Agegnehu

AU - Salas, January

AU - Russell, Kasi

AU - Blanchard, James

AU - Davidow, Amy

AU - Pei, Zhiheng

AU - Chang, Theresa L.

AU - Cheng-Mayer, Cecilia

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N2 - 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. Design/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 infectedmacaques indicates that the femalemacaquesmountedanearlier andmore 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. Conclusion: 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.

AB - 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. Design/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 infectedmacaques indicates that the femalemacaquesmountedanearlier andmore 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. Conclusion: 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.

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