Altered gut microbiota correlate with different immune response to HAART in HIV-infected individuals

Abstract Background: Although gut microbiota dysbiosis has been reported in HIV infected individuals recently, the relationship between the gut microbiota and immune activation in patients with different immune responses to highly active antiretroviral therapy (HAART) is still not well understood. Gut microbiota and immune activation were studied in 36 non-HIV-infected subjects (healthy controls) and 58 HIV-infected individuals, including 28 immunological responders (IR) and 30 immunological non-responders (INR) (≥500 and <200 CD4+ T-cell counts/µl after 2 years of HIV-1 viral suppression respectively) without comorbidities. Results: Metagenome sequencing revealed that HIV-infected immunological responders and immunological non-responders could not recover completely from the gut microbiota dysbiosis. At a 97% similarity level, the relative abundances of Fusobacterium, Ruminococcus gnavus and Megamonas were greater, whereas Faecalibacterium, Alistipes, Bifidobacterium, Eubacterium rectale and Roseburia were more depleted in the IR and INR groups than those in the healthy controls. Ruminococcaceae and Alistipes were positively correlated with nadir and current CD4+ T-cell counts, but negatively correlated with CD8+CD57+ T-cell counts . Inflammation markers and translocation biomarkers (LPS) levels were positively correlated with the abundances of genus Ruminococcus and Fusobacterium but were negatively correlated with the genus Faecalibacterium . The relative abundances of Escherichia-Shigella and Blautia were significantly higher in the IR than those in the INR group. Escherichia-Shigella were negatively correlated with the CD4/CD8 ratio but positively correlated with the amount of C D8+CD57+ T-cells. Roseburia and Blautia were negatively associated with nadir CD4+ T-cell and positively associated with CD8+CD57+ T-cell counts. Conclusions: Gut microbiota dysbiosis may be one of the factors contributing to different immune responses and treatment outcomes to HAART.

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Altered gut microbiota correlate with different immune response to HAART in HIV-infected individuals

10.21203/rs.3.rs-44062/v4 ◽

2020 ◽

Author(s):

Yirui Xie ◽

Jia Sun ◽

Li Wei ◽

Haiyin Jiang ◽

Caiqin Hu ◽

...

Keyword(s):

T Cell ◽

Gut Microbiota ◽

Immune Responses ◽

Immune Activation ◽

Highly Active Antiretroviral Therapy ◽

Cd4 T Cell ◽

Healthy Controls ◽

Cell Counts ◽

Relative Abundances ◽

Gut Microbiota Dysbiosis

Abstract Background: Although gut microbiota dysbiosis has been reported in HIV infected individuals recently, the relationship between the gut microbiota and immune activation in patients with different immune responses to highly active antiretroviral therapy (HAART) is still not well understood. Gut microbiota and immune activation were studied in 36 non-HIV-infected subjects (healthy controls) and 58 HIV-infected individuals, including 28 immunological responders (IR) and 30 immunological non-responders (INR) (≥500 and <200 CD4+ T-cell counts/µl after 2 years of HIV-1 viral suppression respectively) without comorbidities. Results: Metagenome sequencing revealed that HIV-infected immunological responders and immunological non-responders could not recover completely from the gut microbiota dysbiosis. At a 97% similarity level, the relative abundances of Fusobacterium, Ruminococcus gnavus and Megamonas were greater, whereas Faecalibacterium, Alistipes, Bifidobacterium, Eubacterium rectale and Roseburia were more depleted in the IR and INR groups than those in the healthy controls. Ruminococcaceae and Alistipes were positively correlated with nadir and current CD4+ T-cell counts, but negatively correlated with CD8+CD57+ T-cell counts. Inflammation markers and translocation biomarkers (LPS) levels were positively correlated with the abundances of genera Ruminococcus and Fusobacterium but were negatively correlated with the genus Faecalibacterium. The relative abundances of Escherichia-Shigella and Blautia were significantly higher in the IR than those in the INR group. Escherichia-Shigella were negatively correlated with the CD4/CD8 ratio but positively correlated with the amount of CD8+CD57+ T-cells. Roseburia and Blautia were negatively associated with nadir CD4+ T-cell and positively associated with CD8+CD57+ T-cell counts. Conclusions: Gut microbiota dysbiosis may be one of the factors contributing to different immune responses and treatment outcomes to HAART.

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Altered gut microbiota correlate with different immune responses to HAART in HIV-infected individuals

BMC Microbiology ◽

10.1186/s12866-020-02074-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yirui Xie ◽

Jia Sun ◽

Li Wei ◽

Haiyin Jiang ◽

Caiqin Hu ◽

...

Keyword(s):

T Cell ◽

Gut Microbiota ◽

Immune Responses ◽

Immune Activation ◽

Highly Active Antiretroviral Therapy ◽

Cd4 T Cell ◽

Healthy Controls ◽

Cell Counts ◽

Relative Abundances ◽

Gut Microbiota Dysbiosis

Abstract Background Although gut microbiota dysbiosis has been reported in HIV infected individuals recently, the relationship between the gut microbiota and immune activation in patients with different immune responses to highly active antiretroviral therapy (HAART) is still not well understood. Gut microbiota and immune activation were studied in 36 non-HIV-infected subjects (healthy controls) and 58 HIV-infected individuals, including 28 immunological responders (IR) and 30 immunological non-responders (INR) (≥500 and < 200 CD4+ T-cell counts/μl after 2 years of HIV-1 viral suppression respectively) without comorbidities. Results Metagenome sequencing revealed that HIV-infected immunological responders and immunological non-responders could not recover completely from the gut microbiota dysbiosis. At a 97% similarity level, the relative abundances of Fusobacterium, Ruminococcus gnavus and Megamonas were greater, whereas Faecalibacterium, Alistipes, Bifidobacterium, Eubacterium rectale and Roseburia were more depleted in the IR and INR groups than those in the healthy controls. Ruminococcaceae and Alistipes were positively correlated with nadir and current CD4+ T-cell counts, but negatively correlated with CD8 + CD57+ T-cell counts. Inflammation markers and translocation biomarkers (LPS) levels were positively correlated with the abundances of genera Ruminococcus and Fusobacterium but were negatively correlated with the genus Faecalibacterium. The relative abundances of Escherichia-Shigella and Blautia were significantly higher in the IR than those in the INR group. Escherichia-Shigella were negatively correlated with the CD4/CD8 ratio but positively correlated with the amount of CD8 + CD57+ T-cells. Roseburia and Blautia were negatively associated with nadir CD4+ T-cell and positively associated with CD8 + CD57+ T-cell counts. Conclusions Gut microbiota dysbiosis may be one of the factors contributing to different immune responses and treatment outcomes to HAART.

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Altered gut microbiota correlate with different immune response to HAART in HIV-infected individuals

10.21203/rs.3.rs-44062/v2 ◽

2020 ◽

Author(s):

Yirui Xie ◽

Jia Sun ◽

Li Wei ◽

Haiyin Jiang ◽

Caiqin Hu ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Gut Microbiota ◽

Immune Activation ◽

Highly Active Antiretroviral Therapy ◽

Cd4 T Cell ◽

Health Control ◽

Cell Counts ◽

Gut Microbiota Dysbiosis

Abstract Background: Although gut microbiota dysbiosis has recently been reported in HIV infected individuals, the relationship between the gut microbiota and immune activation in patients with a different immune response to highly active antiretroviral therapy (HAART) is still not well understood. Gut microbiota and immune activation were studied in 36 non-HIV-infected subjects (Health Control) and 58 HIV-infected individuals which included 28 immunological responders (IR) and 30 immunological non-responders (INR) (≥500 and <200 CD4+ T-cell counts/µl after 2 years of HIV-1 viral suppression respectively) without comorbidities. Results: Metagenome sequencing revealed that the gut microbiota dysbiosis could not be recovered completely in HIV-infected immunological responders and immunological non-responders although with long-term suppressive antiretroviral treatment. At the 97% similarity level, Fusobacterium, Ruminococcus_gnavus and Megamonas were more abundant, whereas Faecalibacterium, Alistipes, Bifidobacterium, Eubacteriumrectale and Roseburia were more depleted in the IR and INR groups than that in the health control. Ruminococcaceae and Alistipes were positively correlated with nadir and current CD4+ T-cell counts, but negatively correlated with CD8+CD57+ T-cell counts. Inflammation markers and translocation biomarkers (LPS) levels were positively correlated with the abundance of genus Ruminococcus and Fusobacterium, but were negatively correlated with the genus Faecalibacterium. The relative abundances of Escherichia-Shigella and Blautia were significantly higher in the IR than that in the INR group. Escherichia-Shigella were negatively correlated with the CD4/CD8 ratio but positively correlated with the amount of CD8+CD57+ T-cells. Roseburia and Blautia were negatively associated with nadir CD4+ T-cell and positively associated with CD8+CD57+ T-cell counts. Conclusions: Gut microbiota dysbiosis may be one of the factors contributing to different immune response to HAART. Fusobacterium, Alistipes, Ruminococcaceae, Faecalibacterium, Escherichia-Shigella, Roseburia and Blautia maybe the major genus contributed to different immune response in immunodiscordant and immunoconcordant patients on long-term suppressive ART. Blautia and Roseburia might be associated with treatment outcome.

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Altered gut microbiota correlate with different immune response to HAART in HIV-infected individual

10.21203/rs.3.rs-44062/v1 ◽

2020 ◽

Author(s):

Jia Sun ◽

Li Wei ◽

Haiyin Jiang ◽

Caiqin Hu ◽

Jiezuan Yang ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Gut Microbiota ◽

Immune Activation ◽

Highly Active Antiretroviral Therapy ◽

Infected Individual ◽

Cd4 T Cell ◽

Health Control ◽

Cell Counts

Abstract Background: Although gut microbiota dysbiosis has recently been reported in HIV infected individuals, the relationship between the gut microbiota and immune activation in patients with different immune response to highly active antiretroviral therapy (HAART) is still not well understood. Gut microbiota and immune activation were studied in 36 non-HIV-infected subjects (Health Control) and 58 HIV-infected individuals which included 28 immunological responders (IR) and 30 immunological non-responders (INR) (≥500 and <200 CD4+ T-cell counts/µl after 2 years of HIV-1 viral suppression respectively) without comorbidities. Results: Metagenome sequencing revealed that the diversity and composition of gut microbiota could not be recovered completely as normal gut environment in HIV-infected individuals although with immunological response after long-term effective ART. At the genus level, predominant genera Fusobacterium, Ruminococcus_gnavus and Megamonas were more abundant, whereas Faecalibacterium, Alistipes, Bifidobacterium, Eubacteriumrectale, and Roseburia were depleted in IR and INR group than health control. Ruminococcaceae and Alistipes were positively correlated to nadir and current CD4+ T-cell, but negatively correlated to CD8+CD57+ T-cell. Inflammation markers and translocation biomarkers (LPS) levels were positively correlated to the abundance of genus Ruminococcus and Fusobacterium, but were negatively correlated to genus Faecalibacterium. Escherichia-Shigella and Blautia were enriched significantly in IR than INR group. Escherichia-Shigella were negatively correlated to CD4/CD8 ratio, but positively correlated to CD8+CD57+ T-cell. Conclusions: Altogether, the gut microbiota is one of the factors contributing to different immune response to HAART. Fusobacterium, Alistipes, Ruminococcaceae, Faecalibacterium and Escherichia-Shigella maybe the major genus contributed to different immune response in immunodiscordant and immunoconcordant patients on long-term suppressive ART.

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Relation of CD4+CD25+ Regulatory T Cells to Immune Status in Patients with HIV Infection.

Blood ◽

10.1182/blood.v104.11.3106.3106 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3106-3106

Author(s):

Sachi Tsunemi ◽

Tsuyoshi Iwasaki ◽

Takehito Imado ◽

Satoshi Higasa ◽

Eizo Kakishita ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Immune Responses ◽

Hiv Infection ◽

Peripheral Blood ◽

Cd4 T Cells ◽

Cd4 T Cell ◽

Healthy Controls ◽

Cell Counts ◽

Hiv 1

Abstract Human immunodeficiency virus (HIV) infection is characterized by marked defects in CD4+ helper T cell (Th) functions that commonly progress to a substantial decline in peripheral CD4+ T cell counts. However, the mechanisms responsible for the loss of Th functions in HIV-infected patients independent of CD4+ T cell counts remains unclear. CD4+CD25+ regulatory T cells (T Reg) are essential for down-regulation of both autoreactive and alloreactive T cells. Therefore, we decided to investigate the role of T Reg in immune status of HIV-infected patients. We examined the expression of cell surface CD25, cytoplasmic IL-4 and cytoplasmic IFN-gamma in peripheral blood CD4+ T cells from both healthy controls (n=9) and HIV-infected patients (n=43). We also compared T Reg functions between the 2 groups. CD4+CD25+ T Reg isolated from both HIV-infected patients and healthy controls strongly expressed CD45RO, HLA-DR, and FoxP3, and suppressed the proliferation of CD4+CD25− T cells, suggesting that CD4+CD25+ T cells from both healthy controls and HIV-infected patients possess phenotypic and functional characteristics of Treg. CD4+CD25high T cells are a subset of circulating CD4+CD25+ T cells in normal humans and exhibit strong in vitro regulatory functions similar to those reported for murine CD4+CD25+ T Reg. We measured the frequency of CD4+CD25high T Reg by analysis of surface CD25 on CD4+ T cells in peripheral blood samples. We also examined Th1 and Th2 frequencies by analysis of cytoplasmic IFN-gamma and IL-4 levels in CD4+ T cells. T Reg from HIV-infected patients with detectable plasma HIV-1 RNA showed a statistically significant increase in CD4+CD25high cell frequency (p<0.05) compared to healthy controls, with T Reg frequencies inversely proportional to CD4+ T cell numbers (p<0.01). However, in HIV-infected patients with undetectable plasma HIV-RNA, frequencies of CD4+CD25high T Reg were not increased and not related to CD4+ T cell numbers. In both HIV-infected patient groups, T Reg frequency was inversely related to Th1 frequency (detectable: p<0.05, undetectable: p<0.001), but positively related to Th2 frequency (detectable: p<0.01, undetectable: p<0.001). Our results indicate that increased frequencies of peripheral blood T Reg were related to disease progression as measured by detectable plasma HIV-1 RNA, decreased peripheral blood CD4+ T cell counts, and polarization toward Th2 immune responses in HIV-infected patients. HIV infection may lead to induction of T reg that inhibit antiviral immune responses, resulting in the progression of the disease. Manipulation of T Reg could help restore antiviral immune responses in HIV infection, and prevent the progression of HIV infection.

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Persistence of Genital Tract T Cell Responses in HIV-Infected Women on Highly Active Antiretroviral Therapy

Journal of Virology ◽

10.1128/jvi.00518-10 ◽

2010 ◽

Vol 84 (20) ◽

pp. 10765-10772 ◽

Cited By ~ 9

Author(s):

Nonhlanhla N. Mkhize ◽

Pamela P. Gumbi ◽

Lenine J. Liebenberg ◽

Yuan Ren ◽

Peter Smith ◽

...

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Highly Active Antiretroviral Therapy ◽

Genital Tract ◽

T Cell Responses ◽

Antiretroviral Drugs ◽

Cd4 T Cell ◽

Cell Responses ◽

Highly Active ◽

Cell Counts

ABSTRACT Initiation of highly active antiretroviral therapy (HAART) for HIV-infected individuals is associated with control of viremia, improved CD4 counts, and declining systemic HIV-specific immune responses. While HAART effectively reduces plasma viremia, it remains unclear how effectively antiretroviral drugs reach mucosal surfaces, such as those of the genital tract. The aim of this study was to determine the effect of HAART on genital tract CD4 T cell reconstitution, HIV shedding, and HIV-specific T cell responses. Cervical cytobrush and blood specimens were obtained from 35 HIV-infected, HAART-naïve women and 27 women on HAART in order to investigate HIV Gag-specific T cell responses by intracellular gamma interferon (IFN-γ) staining. Interleukin 1β (IL-1β), IL-6, and IL-8 concentrations were measured by enzyme-linked immunosorbent assays (ELISA). We show that for HIV-infected women, HAART is associated with significantly improved CD4 T cell counts both in blood and at the cervix. While HAART effectively suppressed both blood and cervical viremia, HIV-specific CD8 T cell responses in blood were lost, while those at the cervix were preserved.

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