Publications by authors named "Charlene Miller"

Health care delivery science, according to Faerber, "focuses on ways to improve health and services to individuals and populations." The triple aim, described as improving population health, enhancing the care experience, and reducing costs; is a model for health care improvement. In 2014, the triple aim expanded to the quadruple aim to include the health and satisfaction of health care professionals.

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The role of neutrophils relative to vaginal dysbiosis is unclear. We hypothesize that bacterial vaginosis (BV)-associated bacteria may induce the activation and accumulation of mucosal neutrophils within the female reproductive tract (FRT), resulting in epithelial barrier damage. We collected endocervical cytobrushes from women with and without BV and assessed bacteria community type and frequency/functional phenotypes of neutrophils.

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In Sub-Saharan Africa, young women 15-24 years of age account for nearly 30% of all new HIV infections, however, biological and epidemiological factors underlying this disproportionate infection rate are unclear. In this study, we assessed biological contributors of SIV/HIV susceptibility in the female genital tract (FGT) using adolescent ( = 9) and adult ( = 10) pigtail macaques (PTMs) with weekly low-dose intravaginal challenges of SIV. Immunological variables were captured in vaginal tissue of PTMs by flow cytometry and cytokine assays.

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Despite the efficacy of antiretroviral-based pre-exposure prophylactics (PrEP) in men who have sex with men, studies in women have produced widely varying outcomes. Recent evidence demonstrates that vaginal microbial communities are associated with increased HIV acquisition risk and may impact PrEP efficacy. Here, we investigate the mechanisms underlying how vaginal bacteria alter PrEP drug levels and impact HIV infection rates ex vivo.

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The diverse bacterial communities that colonize the gastrointestinal tract play an essential role in maintaining immune homeostasis through the production of critical metabolites such as short-chain fatty acids (SCFAs) and this can be disrupted by antibiotic use. However, few studies have addressed the effects of specific antibiotics longitudinally on the microbiome and immunity. We evaluated the effects of four specific antibiotics: enrofloxacin, cephalexin, paromomycin, and clindamycin, in healthy female rhesus macaques.

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Simian-human immunodeficiency viruses (SHIVs) have been utilized to test vaccine efficacy and characterize mechanisms of viral transmission and pathogenesis. However, the majority of SHIVs currently available have significant limitations in that they were developed using sequences from chronically HIV-infected individuals or uncommon HIV subtypes or were optimized for the macaque model by serially passaging the engineered virus or Recently, a newly developed SHIV, SHIV.C.

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Article Synopsis
  • Gastrointestinal (GI) mucosal dysfunction in HIV infection contributes to health issues and persists despite treatment, partly due to factors that aren't fully understood.
  • Research reveals that increased neutrophil lifespan is linked to neutrophil buildup in the GI tract of HIV patients, suggesting this could be a new target for treatment.
  • The study also shows that the balance of gut bacteria, particularly a lower Lactobacillus to Prevotella ratio, affects neutrophil survival, indicating that restoring beneficial bacteria may help reduce inflammation in HIV and similar chronic conditions.
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The immunological and virological events that contribute to the establishment of Zika virus (ZIKV) infection in humans are unclear. Here, we show that robust cellular innate immune responses arising early in the blood and tissues in response to ZIKV infection are significantly stronger in males and correlate with increased viral persistence. In particular, early peripheral blood recruitment of plasmacytoid dendritic cells and higher production of monocyte chemoattractant protein (MCP-1) correspond with greater viral persistence and tissue dissemination.

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HIV and pathogenic SIV infection are characterized by mucosal dysfunction including epithelial barrier damage, loss of Th17 cells, neutrophil infiltration, and microbial translocation with accompanying inflammation. However, it is unclear how and when these contributing factors occur relative to one another. In order to determine whether any of these features initiates the cycle of damage, we longitudinally evaluated the kinetics of mucosal and systemic T-cell activation, microbial translocation, and Th17 cell and neutrophil frequencies following intrarectal SIV infection of rhesus macaques.

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Background: Cannabis is a widely used drug in the United States, and the frequency of cannabis use in the human immunodeficiency virus (HIV)-infected population is disproportionately high. Previous human and macaque studies suggest that cannabis may have an impact on plasma viral load; however, the relationship between cannabis use and HIV-associated systemic inflammation and immune activation has not been well defined.

Methods: The impact of cannabis use on peripheral immune cell frequency, activation, and function was assessed in 198 HIV-infected, antiretroviral-treated individuals by flow cytometry.

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Article Synopsis
  • Liver disease significantly impacts individuals with HIV, even with combination antiretroviral therapy (cART), but the underlying mechanisms remain unclear due to challenges in human sample collection and confounding factors like co-infections.
  • A study using SIV-infected macaques found that untreated infection led to increased levels of liver macrophages and various inflammatory mediators, indicating a strong immune response linked to liver inflammation.
  • In macaques receiving cART, there were reduced levels of liver macrophages and inflammation, but residual SIV DNA and bacterial DNA suggest ongoing immune activation in the liver despite treatment.
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Antibiotic therapies are known to disrupt gastrointestinal (GI) bacterial communities. HIV and pathogenic simian immunodeficiency virus (SIV) infections have also been associated with disrupted GI bacterial communities. We administered a combination antibiotic therapy to six SIV-infected rhesus macaques and collected colon biopsies, stool samples and rectal swabs before and after antibiotics, and evaluated the bacterial communities at each sample site using high-throughput 16S rRNA gene sequencing.

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The mesenteric lymph nodes (MLN) and the liver are exposed to microbes and microbial products from the gastrointestinal (GI) tract, making them immunologically unique. The GI tract and associated MLN are sites of early viral replication in human immunodeficiency virus (HIV) infection and the MLN are likely important reservoir sites that harbor latently-infected cells even after prolonged antiretroviral therapy (ART). The liver has been shown to play a significant role in immune responses to lentiviruses and appears to play a significant role in clearance of virus from circulation.

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Unlabelled: An altered intestinal microbiome during chronic human immunodeficiency virus (HIV) infection is associated with mucosal dysfunction, inflammation, and disease progression. We performed a preclinical evaluation of the safety and efficacy of fecal microbiota transplantation (FMT) as a potential therapeutic in HIV-infected individuals. Antiretroviral-treated, chronically simian immunodeficiency virus (SIV)-infected rhesus macaques received antibiotics followed by FMT.

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Given the critical role of mucosal surfaces in susceptibility to infection, it is imperative that effective mucosal responses are induced when developing efficacious vaccines and prevention strategies for infection. Modulating the microbiota in the gastrointestinal (GI) tract through the use of probiotics (PBio) is a safe and well-tolerated approach to enhance mucosal and overall health. We assessed the longitudinal impact of daily treatment with the VSL#3 probiotic on cellular and humoral immunity and inflammation in healthy macaques.

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Anthocyanins in upper (adaxial) leaf tissues provide greater photoprotection than in lower (abaxial) tissues, but also predispose tissues to increased shade acclimation and, consequently, reduced photosynthetic capacity. Abaxial anthocyanins may be a compromise between these costs/benefits. Plants adapted to shaded understory environments often exhibit red/purple anthocyanin pigmentation in lower (abaxial) leaf surfaces, but rarely in upper (adaxial) surfaces.

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