scholarly journals Liver Bacterial Dysbiosis With Non-Tuberculosis Mycobacteria Occurs in SIV-Infected Macaques and Persists During Antiretroviral Therapy

2022 ◽  
Vol 12 ◽  
Author(s):  
Bridget S. Fisher ◽  
Katherine A. Fancher ◽  
Andrew T. Gustin ◽  
Cole Fisher ◽  
Matthew P. Wood ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Relative Abundance ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Phosphatidyl Inositol ◽  
Opportunistic Pathogen ◽  
Atypical Mycobacteria ◽  
Microbial Composition ◽  
Transcriptional Responses ◽  
Pass Through

Liver disease is a significant contributor to morbidity and mortality in HIV-infected individuals, even during successful viral suppression with combination antiretroviral therapy (cART). Similar to HIV infection, SIV infection of rhesus macaques is associated with gut microbiome dysbiosis and microbial translocation that can be detected systemically in the blood. As microbes leaving the intestines must first pass through the liver via the portal vein, we evaluated the livers of both SIV-infected (SIV+) and SIV-infected cART treated (SIV+cART) rhesus macaques for evidence of microbial changes compared to uninfected macaques. Dysbiosis was observed in both the SIV+ and SIV+cART macaques, encompassing changes in the relative abundance of several genera, including a reduction in the levels of Lactobacillus and Staphylococcus. Most strikingly, we found an increase in the relative abundance and absolute quantity of bacteria within the Mycobacterium genus in both SIV+ and SIV+cART macaques. Multi-gene sequencing identified a species of atypical mycobacteria similar to the opportunistic pathogen M. smegmatis. Phosphatidyl inositol lipoarabinomannan (PILAM) (a glycolipid cell wall component found in atypical mycobacteria) stimulation in primary human hepatocytes resulted in an upregulation of inflammatory transcriptional responses, including an increase in the chemokines associated with neutrophil recruitment (CXCL1, CXCL5, and CXCL6). These studies provide key insights into SIV associated changes in hepatic microbial composition and indicate a link between microbial components and immune cell recruitment in SIV+ and SIV+cART treated macaques.

scholarly journals Liver bacterial dysbiosis occurs in SIV-infected macaques and persists during antiretroviral therapy

2020 ◽  
Author(s):  
Bridget S Fisher ◽  
Katherine A Fancher ◽  
Andrew T Gustin ◽  
Cole Fisher ◽  
Matthew P Wood ◽  
...  
Keyword(s):  
Liver Disease ◽  
Antiretroviral Therapy ◽  
Inflammatory Responses ◽  
Rhesus Macaques ◽  
Neutrophil Infiltration ◽  
Opportunistic Pathogen ◽  
Environmental Mycobacteria ◽  
Siv Infection ◽  
Abundant Genus

Abstract Background: Liver disease remains a significant contributor to morbidity and mortality in HIV-infected individuals, even during successful treatment with combination antiretroviral therapy (cART). In non-human primates, SIV infection is associated with gut microbiome dysbiosis as well as bacterial translocation into the colonic lamina propria and liver via the portal vein. Here the liver microbiome was evaluated in rhesus macaques to discern the influence of SIV infection alone (SIV+) and during cART administration (SIV+cART) on liver bacterial dysbiosis and neutrophil infiltration.Results: Dysbiosis in liver bacterial composition was observed, encompassing changes in a number of genera, during SIV infection in the absence and presence of cART. The most striking finding was an increase in the level of Mycobacterium, which while barely detectable in the uninfected macaques, was the most abundant genus observed in the livers of a majority SIV+ and SIV+cART macaques. Multi-gene sequencing analyses identified a species of environmental mycobacteria similar to the opportunistic pathogen M. smegmatis. The effect of M. smegmatis on host gene expression in primary hepatocytes was evaluated in vitro utilizing PILAM, a glycolipid cell wall component found in atypical Mycobacteria. PILAM induced an upregulation of inflammatory responses, including an increase in the chemokines associated with neutrophil chemotaxis (CXCL1, CXCL5, and CXCL6). Assessment of the macaque livers by microscopy determined that neutrophil levels were reduced in SIV+cART macaques, suggesting that the SIV infection and/or cART treatment influence the liver-associated neutrophil response. Conclusions: A number of liver bacteria genera were altered following SIV infection even in the context of cART, possibly as a consequence of reduced neutrophil recruitment. Mycobacteria became a major component of the SIV infected macaque liver microbiome, raising the possibility that bacteria of this genus might contribute to liver disease in HIV infected patients.

scholarly journals CD8+ lymphocytes modulate Zika virus dynamics and tissue dissemination and orchestrate antiviral immunity

2018 ◽  
Author(s):  
Blake Schouest ◽  
Marissa Fahlberg ◽  
Elizabeth A. Scheef ◽  
Matthew J. Ward ◽  
Kyra Headrick ◽  
...  
Keyword(s):  
Immune Responses ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Viral Infections ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Acute Infection ◽  
Transcriptional Responses ◽  
Adaptive Immune ◽  
Cd8 Depletion

AbstractCD8+ lymphocytes are critically important in the control of viral infections, but their roles in acute Zika virus (ZIKV) infection remain incompletely explored in a model sufficiently similar to humans immunologically. Here, we use CD8+ lymphocyte depletion to dissect acute immune responses in adult male rhesus and cynomolgus macaques infected with ZIKV. CD8 depletion delayed serum viremia and dysregulated patterns of innate immune cell homing and monocyte-driven transcriptional responses in the blood. CD8-depleted macaques also showed evidence of compensatory adaptive immune responses, with elevated Th1 activity and persistence of neutralizing antibodies beyond the clearance of serum viremia. The absence of CD8+ lymphocytes increased viral burdens in lymphatic tissues, semen, and cerebrospinal fluid, and neural lesions were also evident in both CD8-depleted rhesus macaques. Together, these data support a role for CD8+ lymphocytes in the control of ZIKV dissemination and in maintaining immune regulation during acute infection of nonhuman primates.

scholarly journals Metatranscriptomic analysis of colonic microbiota’s functional response to different dietary fibers in growing pigs

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Jie Xu ◽  
Rongying Xu ◽  
Menglan Jia ◽  
Yong Su ◽  
Weiyun Zhu
Keyword(s):  
Gene Expression ◽  
Functional Response ◽  
Relative Abundance ◽  
Expression Profiles ◽  
Nutrient Digestibility ◽  
Growing Pigs ◽  
Control Group ◽  
Dietary Fibers ◽  
Microbial Composition ◽  
Colonic Microbiota

Abstract Background Dietary fibers are widely considered to be beneficial to health as they produce nutrients through gut microbial fermentation while facilitating weight management and boosting gut health. To date, the gene expression profiles of the carbohydrate active enzymes (CAZymes) that respond to different types of fibers (raw potato starch, RPS; inulin, INU; pectin, PEC) in the gut microbes of pigs are not well understood. Therefore, we investigated the functional response of colonic microbiota to different dietary fibers in pigs through metatranscriptomic analysis. Results The results showed that the microbial composition and CAZyme structure of the three experimental groups changed significantly compared with the control group (CON). Based on a comparative analysis with the control diet, RPS increased the abundance of Parabacteroides, Ruminococcus, Faecalibacterium and Alloprevotella but decreased Sutterella; INU increased the relative abundance of Fusobacterium and Rhodococcus but decreased Bacillus; and PEC increased the relative abundance of the Streptococcus and Bacteroidetes groups but decreased Clostridium, Clostridioides, Intestinibacter, Gemmiger, Muribaculum and Vibrio. The gene expression of CAZymes GH8, GH14, GH24, GH38, GT14, GT31, GT77 and GT91 downregulated but that of GH77, GH97, GT3, GT10 and GT27 upregulated in the RPS diet group; the gene expression of AA4, AA7, GH14, GH15, GH24, GH26, GH27, GH38, GH101, GT26, GT27 and GT38 downregulated in the INU group; and the gene expression of PL4, AA1, GT32, GH18, GH37, GH101 and GH112 downregulated but that of CE14, AA3, AA12, GH5, GH102 and GH103 upregulated in the PEC group. Compared with the RPS and INU groups, the composition of colonic microbiota in the PEC group exhibited more diverse changes with the variation of CAZymes and Streptococcus as the main contributor to CBM61, which greatly promoted the digestion of pectin. Conclusion The results of this exploratory study provided a comprehensive overview of the effects of different fibers on nutrient digestibility, gut microbiota and CAZymes in pig colon, which will furnish new insights into the impacts of the use of dietary fibers on animal and human health.

scholarly journals Impact of the gut microbiome on the atorvastatin-dependent modulation of the serum lipidome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Roessler ◽  
F Zimmermann ◽  
D Schmidt ◽  
U Escher ◽  
A Jasina ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Interindividual Variation ◽  
Funding Source ◽  
Microbial Composition ◽  
Atorvastatin Treatment ◽  
Qrt Pcr ◽  
16S Rna ◽  
Regulatory Properties

Abstract Background and aims The modulation of serum lipids, in particular of the low-density lipoprotein cholesterol (LDL-C), by statins varies between individuals. The mechanisms regulating this interindividual variation are only poorly understood. Here, we investigated the relation between the gut microbiome and the regulatory properties of atorvastatin on the serum lipidome using mice with depleted gut microbiome. Methods Over a period of 6 weeks, mice (C57BL/6) with either an intact (conventional mice, CONV, n=24) or antibiotic-based depleted gut microbiome (antibiotic treated mice, ABS, n=16) were put on standard chow diet (SCD) or high fat diet (HFD), respectively. During the last 4 weeks of treatment atorvastatin (Ator, 10mg/kg body weight/day) or control vehicle was administered via daily oral gavage. Blood lipids (total cholesterol, VLDL, LDL-C, HDL-C) and serum sphingolipids were compared among the groups. The expressions of hepatic and intestinal genes involved in cholesterol metabolism were analyzed by qRT-PCR. Alterations in the gut microbiota profile of mice with intact gut microbiome were examined using 16S RNA qRT-PCR. Results In CONV mice, HFD led to significantly increased blood LDL-C levels as compared with SCD (HFD: 36.8±1.4 mg/dl vs. SCD: 22.0±1.8 mg/dl; P<0.01). In CONV mice atorvastatin treatment significantly reduced blood LDL-C levels after HFD, whereas in ABS mice the LDL-C lowering effect of atorvastatin was markedly attenuated (CONV+HFD+Ator: 31.0±1.8 mg/dl vs. ABS+HFD+Ator: 46.4±3 mg/dl; P<0.01). A significant reduction in the abundance of several plasma lipids, in particular sphingolipids and glycerophospholipids upon atorvastatin treatment was observed in CONV mice, but not in ABS mice. The expressions of distinct hepatic and intestinal cholesterol-regulating genes (ldlr, srebp2, pcsk9 and npc1l1) upon atorvastatin treatment were significantly altered in gut microbiota depleted mice. In response to HFD a decrease in the relative abundance of the bacterial phyla Bacteroides and an increase in the relative abundance of Firmicutes was observed. The altered ratio between Bacteroides and Firmicutes in HFD fed mice was partly reversed upon atorvastatin treatment. Conclusions Our findings indicate a crucial role of the gut microbiome for the regulatory properties of atorvastatin on the serum lipidome and, in turn, support a critical impact of atorvastatin on the gut microbial composition. The results provide novel insights into potential microbiota related mechanisms underlying interindividual variation in modulation of the serum lipidome by statins, given interindividual differences in microbiome composition and function. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): German Heart Research Foundation

scholarly journals Transient viral replication during analytical treatment interruptions in SIV infected macaques can alter the rebound-competent viral reservoir

2021 ◽  
Vol 17 (6) ◽  
pp. e1009686
Author(s):  
Taina T. Immonen ◽  
Christine M. Fennessey ◽  
Leslie Lipkey ◽  
Abigail Thorpe ◽  
Gregory Q. Del Prete ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Viral Replication ◽  
Rhesus Macaques ◽  
Treatment Strategies ◽  
Viral Reservoir ◽  
Virus Population ◽  
Analytical Treatment ◽  
Treatment Interruptions ◽  
The Impact ◽  
Hiv 1

Analytical treatment interruptions (ATIs) of antiretroviral therapy (ART) play a central role in evaluating the efficacy of HIV-1 treatment strategies targeting virus that persists despite ART. However, it remains unclear if ATIs alter the rebound-competent viral reservoir (RCVR), the virus population that persists during ART and from which viral recrudescence originates after ART discontinuation. To assess the impact of ATIs on the RCVR, we used a barcode sequence tagged SIV to track individual viral lineages through a series of ATIs in Rhesus macaques. We demonstrate that transient replication of individual rebounding lineages during an ATI can lead to their enrichment in the RCVR, increasing their probability of reactivating again after treatment discontinuation. These data establish that the RCVR can be altered by uncontrolled replication during ATI.

scholarly journals Immune Cell-Derived Extracellular Vesicles – New Strategies in Cancer Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Pengxiang Yang ◽  
Yong Peng ◽  
Yuan Feng ◽  
Zhuoying Xu ◽  
Panfeng Feng ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Immune Cell ◽  
Bilayer Membrane ◽  
Innate Immune ◽  
Antitumor Effects ◽  
Comprehensive Overview ◽  
Surface Receptors ◽  
Effector Molecules ◽  
Therapeutic Modalities ◽  
Pass Through

Immune cell-derived extracellular vesicles (EVs) have increasingly become the focus of research due to their unique characteristics and bioinspired applications. They are lipid bilayer membrane nanosized vesicles harboring a range of immune cell-derived surface receptors and effector molecules from parental cells. Immune cell-derived EVs are important mediators of intercellular communication that regulate specific mechanisms of adaptive and innate immune responses. However, the mechanisms underlying the antitumor effects of EVs are still being explored. Importantly, immune cell-derived EVs have some unique features, including accessibility, storage, ability to pass through blood-brain and blood-tumor barriers, and loading of various effector molecules. Immune cell-derived EVs have been directly applied or engineered as potent antitumor vaccines or for the diagnosis of clinical diseases. More research applications involving genetic engineering, membrane engineering, and cargo delivery strategies have improved the treatment efficacy of EVs. Immune cell-derived EV-based therapies are expected to become a separate technique or to complement immunotherapy, radiotherapy, chemotherapy and other therapeutic modalities. This review aims to provide a comprehensive overview of the characteristics and functions of immune cell-derived EVs derived from adaptive (CD4+ T, CD8+ T and B cells) and innate immune cells (macrophages, NK cells, DCs, and neutrophils) and discuss emerging therapeutic opportunities and prospects in cancer treatment.

scholarly journals Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques

2019 ◽  
Vol 117 (38) ◽  
pp. 23317-23322 ◽  
Author(s):  
Joaquín Sanz ◽  
Paul L. Maurizio ◽  
Noah Snyder-Mackler ◽  
Noah D. Simons ◽  
Tawni Voyles ◽  
...  
Keyword(s):  
Gene Expression ◽  
Social Status ◽  
Social History ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Expression Patterns ◽  
Social Experience ◽  
Type I ◽  
Gene Expression Response ◽  
Expression Of Genes

Social experience is an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a proinflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. Here we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. As predicted by current models, bacterial lipopolysaccharide polarizes the immune response such that low status corresponds to higher expression of genes in NF-κB–dependent proinflammatory pathways and lower expression of genes involved in the antiviral response and type I IFN signaling. Counter to predictions, however, low status drives more exaggerated expression of both NF-κB– and IFN-associated genes after cells are exposed to the viral mimic Gardiquimod. Status-driven gene expression patterns are linked not only to social status at the time of sampling, but also to social history (i.e., past social status), especially in unstimulated cells. However, for a subset of genes, we observed interaction effects in which females who fell in rank were more strongly affected by current social status than those who climbed the social hierarchy. Taken together, our results indicate that the effects of social status on immune cell gene expression depend on pathogen exposure, pathogen type, and social history—in support of social experience-mediated biological embedding in adulthood, even in the conventionally memory-less innate immune system.

scholarly journals Training rhesus macaques to take daily oral antiretroviral therapy for preclinical evaluation of HIV prevention and treatment strategies

PLoS ONE ◽  
2019 ◽  
Vol 14 (11) ◽  
pp. e0225146
Author(s):  
Michele B. Daly ◽  
April M. Clayton ◽  
Susan Ruone ◽  
James Mitchell ◽  
Chuong Dinh ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Prevention ◽  
Rhesus Macaques ◽  
Treatment Strategies ◽  
Preclinical Evaluation ◽  
Prevention And Treatment

scholarly journals Decreased Snow Cover Stimulates Under-Ice Primary Producers but Impairs Methanotrophic Capacity

mSphere ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Sarahi L. Garcia ◽  
Anna J. Szekely ◽  
Christoffer Bergvall ◽  
Martha Schattenhofer ◽  
Sari Peura
Keyword(s):  
Climate Change ◽  
Snow Cover ◽  
Water Column ◽  
Relative Abundance ◽  
Heterotrophic Bacteria ◽  
Methane Emissions ◽  
Boreal Lakes ◽  
Climate Change Scenarios ◽  
Primary Producers ◽  
Microbial Composition

ABSTRACT Climate change scenarios anticipate decreased spring snow cover in boreal and subarctic regions. Forest lakes are abundant in these regions and substantial contributors of methane emissions. To investigate the effect of reduced snow cover, we experimentally removed snow from an anoxic frozen lake. We observed that the removal of snow increased light penetration through the ice, increasing water temperature and modifying microbial composition in the different depths. Chlorophyll a and b concentrations increased in the upper water column, suggesting activation of algal primary producers. At the same time, Chlorobiaceae, one of the key photosynthetic bacterial families in anoxic lakes, shifted to lower depths. Moreover, a decrease in the relative abundance of methanotrophs within the bacterial family Methylococcaceae was detected, concurrent with an increase in methane concentration in the water column. These results indicate that decreased snow cover impacts both primary production and methane production and/or consumption, which may ultimately lead to increased methane emissions after spring ice off. IMPORTANCE Small lakes are an important source of greenhouse gases in the boreal zone. These lakes are severely impacted by the winter season, when ice and snow cover obstruct gas exchange between the lake and the atmosphere and diminish light availability in the water column. Currently, climate change is resulting in reduced spring snow cover. A short-term removal of the snow from the ice stimulated algal primary producers and subsequently heterotrophic bacteria. Concurrently, the relative abundance of methanotrophic bacteria decreased and methane concentrations increased. Our results increase the general knowledge of microbial life under ice and, specifically, the understanding of the potential impact of climate change on boreal lakes.

Sign in / Sign up

Export Citation Format

Share Document