Alan Landay

Rush University Medical Center, Chicago, Illinois, United States

Are you Alan Landay?

Claim your profile

Publications (395)2265.86 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: HIV-1-associated disruption of intestinal homeostasis is a major factor contributing to chronic immune activation and inflammation. Dendritic cells (DCs) are crucial in maintaining intestinal homeostasis, but the impact of HIV-1 infection on intestinal DC number and function has not been extensively studied. We compared the frequency and activation/maturation status of colonic myeloid DC (mDC) subsets (CD1c(+) and CD1c(neg)) and plasmacytoid DCs in untreated HIV-1-infected subjects with uninfected controls. Colonic mDCs in HIV-1-infected subjects had increased CD40 but decreased CD83 expression, and CD40 expression on CD1c(+) mDCs positively correlated with mucosal HIV-1 viral load, with mucosal and systemic cytokine production, and with frequencies of activated colon and blood T cells. Percentage of CD83(+)CD1c(+) mDCs negatively correlated with frequencies of interferon-γ-producing colon CD4(+) and CD8(+) T cells. CD40 expression on CD1c(+) mDCs positively associated with abundance of high prevalence mucosal Prevotella copri and Prevotella stercorea but negatively associated with a number of low prevalence mucosal species, including Rumminococcus bromii. CD1c(+) mDC cytokine production was greater in response to in vitro stimulation with Prevotella species relative to R. bromii. These findings suggest that, during HIV infection, colonic mDCs become activated upon exposure to mucosal pathobiont bacteria leading to mucosal and systemic immune activation.Mucosal Immunology advance online publication, 29 April 2015; doi:10.1038/mi.2015.33.
    Mucosal Immunology 04/2015; DOI:10.1038/mi.2015.33 · 7.54 Impact Factor
  • Clinical Infectious Diseases 04/2015; DOI:10.1093/cid/civ325 · 9.42 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tissue factor (TF) is a protein that mediates the initiation of the coagulation cascade. TF expression is increased in patients with poorly-controlled HIV, and may be associated with increased immune activation that leads to cardiovascular morbidity. The role of TF in immune activation in liver disease in hepatitis C virus (HCV)-monoinfection and HIV/HCV-coinfection has not been explored. Fifty-nine patients were stratified: A) HIV-monoinfection (N = 15), B) HCV-monoinfection with chronic hepatitis C (CHC) (N = 15), C) HIV/HCV-coinfection with CHC (N = 14), and D) HIV/HCV-seropositive with cleared-HCV (N = 15). All HIV+ patients had undetectable HIV viremia. Whole blood was collected for CD4/CD8 immune activation markers by flow cytometry and plasma was assayed for microparticle TF (MPTF) activity. Subjects underwent transient elastography (TE) to stage liver fibrosis. Undetectable versus detectable MPTF was compared across strata using Fisher's Exact test. MPTF activity was more frequently detected among patients with HCV-monoinfection (40%), compared to HIV-monoinfection and HIV/HCV-seropositive with cleared HCV (7%) and HIV/HCV-coinfection with CHC (14%)(p = 0.02). Mean TE-derived liver stiffness score in kPa was higher in patients with detectable MPTF (12.4 ± 8.5) than those with undetectable MPTF (6.4 ± 3.0)(p = 0.01). Mean CD4 + HLADR+ and CD4 + CD38-HLADR+ expression were higher in those with detectable MPTF (44 ± 9.8% and 38 ± 8.7%, respectively) than those with undetectable MPTF (36 ± 11% and 31 ± 10.4% respectively)(p = 0.05 and 0.04 respectively). HCV-monoinfection and HIV/HCV-coinfection with CHC were associated with MPTF activity. MPTF activity is also associated with advanced liver fibrosis and with CD4 + HLADR+ immune activation.
    BMC Infectious Diseases 04/2015; 15(1):190. DOI:10.1186/s12879-015-0920-1 · 2.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: All-cause mortality and serious non-AIDS events (SNAEs) in individuals with HIV-1 infection receiving antiretroviral therapy are associated with increased production of interleukin-6 which appears to be driven by monocyte/macrophage activation. Plasma levels of other cytokines or chemokines associated with immune activation might also be biomarkers of an increased risk of mortality and/or SNAEs. Baseline plasma samples from 142 participants enrolled into the Strategies for Management of Antiretroviral Therapy study, who subsequently died, and 284 matched controls, were assayed for levels of 15 cytokines and chemokines. Cytokine and chemokine levels were analysed individually and when grouped according to function (innate/proinflammatory response, cell trafficking and cell activation/proliferation) for their association with the risk of subsequent death. Higher plasma levels of proinflammatory cytokines (interleukin-6 and tumour necrosis factor-α) were associated with an increased risk of all-cause mortality but in analyses adjusted for potential confounders, only the association with interleukin-6 persisted. Increased plasma levels of the chemokine CXCL8 were also associated with all-cause mortality independently of hepatitis C virus status but not when analyses were adjusted for all confounders. In contrast, higher plasma levels of cytokines mediating cell activation/proliferation were not associated with a higher mortality risk and exhibited a weak protective effect when analysed as a group. Whereas plasma levels of interleukin-6 are the most informative biomarker of cytokine dysregulation associated with all-cause mortality in individuals with HIV-1 infection, assessment of plasma levels of CXCL8 might provide information about causes of mortality and possibly SNAEs.
    AIDS (London, England) 02/2015; DOI:10.1097/QAD.0000000000000618 · 6.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic inflammation and immune activation occur in both HIV infection and normal ageing and are associated with inflammatory disease. However, the degree to which HIV influences age-related innate immune changes, and the biomarkers which best reflect them, remains unclear. We measured established innate immune ageing biomarkers in 309 individuals including 88 virologically-suppressed (VS) and 52 viremic (viral load ≤ and >50 copies/ml respectively) HIV+ individuals. Levels of soluble (ie. CXCL10, soluble CD163, neopterin) and cellular (ie. proportions of inflammatory CD16+ monocytes) biomarkers of monocyte activation were increased in HIV+ individuals and were only partially ameliorated by viral suppression. Viremic and VS HIV+ individuals show levels of age-related monocyte activation biomarkers that are similar to uninfected controls aged 12 and 4 years older respectively. Viremic HIV infection was associated with an accelerated rate of change of some monocyte activation markers (eg. neopterin) with age, whilst in VS individuals, subsequent age-related changes occurred at a similar rate as in controls, albeit at a higher absolute level. We further identified CXCL10 as a robust soluble biomarker of monocyte activation, highlighting the potential utility of this chemokine as a prognostic marker. These findings may partially explain the increased prevalence of inflammatory, age-related diseases in HIV+ individuals and potentially indicate the pathological mechanisms underlying these diseases which persist despite viral suppression.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2015; DOI:10.1097/QAI.0000000000000559 · 4.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: With the advent of antiretroviral therapy that can control virus replication below the detection levels of conventional assays, a new clinical landscape of AIDS emerged, in which non-AIDS complications prevail over AIDS-defining conditions. These comorbidities are diverse and affect multiple organs, thus resulting in cardiovascular, kidney, neurocognitive and liver disease, osteopenia/osteoporosis, and cancers. A common feature of these conditions is that they are generally associated with accelerated aging. The mechanism behind these comorbidities is chronic excessive inflammation induced by HIV infection, which persists under antiretroviral therapy. Progressive simian immunodeficiency virus (SIV) infection of nonhuman primates (NHPs) closely reproduces these comorbidities and offers a simplified system in which most of the traditional human risk factors for comorbidities (i.e., smoking, hyperlipidemia) are absent. Additionally, experimental conditions can be properly controlled during a shorter course of disease for SIV infection. As such, NHPs can be employed to characterize new paradigms of AIDS pathogenesis and to test the efficacy of interventions aimed at alleviating non-AIDS-related comorbidities.
    Current HIV/AIDS Reports 01/2015; 12(1). DOI:10.1007/s11904-014-0245-5
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite the use of HAART to control HIV, systemic immune activation and inflammation persists with the consequence of developing serious non-AIDS events. The mechanisms that contribute to persistent systemic immune activation have not been well defined. The intestine is the major source of "sterile" inflammation and plays a critical role in immune function; thus, we sought to determine whether intestinal gene expression was altered in virally controlled HIV+ individuals. Gene expression was compared in biopsy samples collected from HIV- and HIV+ individuals from the ileum, right colon (ascending colon), and left colon (sigmoid). Affymetrix gene arrays were performed on tissues and pathway analyses were conducted. Gene expression was correlated with systemic markers of intestinal barrier dysfunction and inflammation and intestinal microbiota composition. Genes involved in cellular immune response, cytokine signaling, pathogen-influenced signaling, humoral immune response, apoptosis, intracellular and second messenger signaling, cancer, organismal growth and development, and proliferation and development were upregulated in the intestine of HIV+ individuals with differences observed in the ileum, right, and left colon. Gene expression in the ileum primarily correlated with systemic markers of inflammation (e.g., IL7R, IL2, and TLR2 with serum TNF) whereas expression in the colon correlated with the microbiota community (e.g., IFNG, IL1B, and CD3G with Bacteroides). These data demonstrate persistent, proinflammatory changes in the intestinal mucosa of virally suppressed HIV+ individuals. These changes in intestinal gene expression may be the consequence of or contribute to barrier dysfunction and intestinal dysbiosis observed in HIV.
    AIDS (London, England) 01/2015; DOI:10.1097/QAD.0000000000000569 · 6.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/μl, bias ranged from -35.2 to +13.1 cells/μl while at counts >350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed.
    PLoS ONE 01/2015; 10(3):e0115019. DOI:10.1371/journal.pone.0115019 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin-8 (IL-8, CXCL8) plays important roles in immune responses at mucosal sites including in the lower genital tract. Since several types of bacteria produce proteases that cleave IL-8 and many types of bacteria can be present in lower genital tract microbiota, we assessed genital fluids for IL-8 cleavage/alteration. Genital fluids collected by lavage from 200 women (23 HIV-seronegative and 177 HIV-seropositive) were tested for IL-8 cleavage/alteration by ELISA. IL-8 cleaving/altering activity was observed in fluids from both HIV-positive (28%) and HIV-negative women (35%). There was no clear relationship between the activity and the types of bacteria present in the lower genital tract as determined by high-throughput sequencing of the 16S rRNA gene. Protease inhibitors specific for matrix metalloproteinases (MMPs) reduced the activity and a multiplex assay that detects both inactive and active MMPs showed the presence of multiple MMPs, including MMP-1, -3, -7, -8, -9, -10 and -12 in genital secretions from many of the women. The IL-8-cleaving/altering activity significantly correlated with active MMP-9 as well as with cleavage of a substrate that is acted on by several active MMPs. These studies show that multiple MMPs are present in the genital tract of women and strongly suggest that MMP-9 in genital secretions can cleave IL-8 at this mucosal site. These studies suggest that MMP-mediated cleavage of IL-8 can modulate inflammatory responses in the lower genital tract.
    PLoS ONE 01/2015; 10(1):e0116911. DOI:10.1371/journal.pone.0116911 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have suggested that glycogen expression in the vaginal epithelium decreases during menopause, resulting in reduced levels of lactobacilli. However, free glycogen in genital fluids and its relationship with Lactobacillus levels have not been compared in premenopausal and postmenopausal women. Eighty-two cervicovaginal lavage samples were collected at different phases of the menstrual cycle from 11 premenopausal (4 HIV-uninfected and 7 HIV-infected) and 12 postmenopausal (7 HIV-uninfected and 5 HIV-infected) women during a 1- to 3-month period. Free glycogen was quantified in genital fluids. Lactobacillus levels were quantified by real-time polymerase chain reaction. Estrogen and progesterone levels in blood were determined by enzyme-linked immunosorbent assay. Free glycogen was detected in both premenopausal and postmenopausal women. Across all samples, those from postmenopausal women had significantly lower levels of free glycogen than those from premenopausal women (median, 0.002 vs 0.065 μg/μL, respectively; P = 0.03). Lactobacillus levels correlated positively with free glycogen in both premenopausal (Spearman r = 0.68, P < 0.0001) and postmenopausal (r = 0.60, P < 0.002) women. Samples from premenopausal women had higher Lactobacillus levels and lower vaginal pH (median log, 8.1; median pH, 4) than those from postmenopausal women (median log, 7.1; median pH, 4.6), although these differences were not significant. HIV status had no significant effect on these relationships. Free glycogen is detected in both premenopausal and postmenopausal women and correlates with Lactobacillus in both groups. These results point to the complexity of the relationship between menopause and vaginal microbiota and indicate that more careful studies of the role of glycogen are warranted.
    Menopause (New York, N.Y.) 12/2014; DOI:10.1097/GME.0000000000000397 · 2.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abnormal levels of inflammation are associated with cardiovascular disease and mortality in human immunodeficiency virus (HIV)-infected patients. Microbial translocation, which may cause inflammation, is decreased by sevelamer in patients undergoing hemodialysis. In this single-arm study, we evaluated the effects of 8 weeks of sevelamer therapy on 36 HIV-infected subjects who were not receiving antiretroviral therapy. Sevelamer did not significantly change markers of microbial translocation, inflammation, or T-cell activation. During sevelamer treatment, however, levels of soluble tissue factor, low-density lipoprotein (LDL) cholesterol, and oxidized LDL cholesterol decreased significantly, whereas D-dimer levels increased. Thus, in this study population, sevelamer did not reduce microbial translocation but may have yielded cardiovascular benefits.
    The Journal of Infectious Diseases 11/2014; 210(10). DOI:10.1093/infdis/jiu305 · 5.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Investigations into apoptotic pathways, intrinsic and extrinsic, and the effects of highly active antiretroviral therapy (HAART) on T cell death via those pathways may provide insight into the mechanisms of and barriers to immune recovery. HIV-1-infected patients were enrolled into a randomized, controlled study of the immune effects of a lopinavir/ritonavir (LPV/r)-based versus an efavirenz (EFV)-based HAART regimen in antiretroviral-naive subjects with CD4(+) counts <350 cells/mm(3). Patients were randomized to receive TDF/FTC/EFZ or TDF/FTC plus LPV/r. Fourteen patients were enrolled and 10 patients completed 6 months of therapy as per the protocol. CD4(+) counts were measured before and during HAART therapy. We isolated T cell subsets to measure ex vivo apoptosis by propidium iodide staining. We also assessed caspase activation for the intrinsic and extrinsic pathways of apoptosis, as well as effector caspase activation. We also measured mitochondrial membrane potential. Cells were analyzed by flow cytometry. All patients had increased activation of caspase 8 (extrinsic pathway), caspase 9 (intrinsic pathway), effector caspases 3/7, and low mitochondrial membrane potential at baseline compared to controls. By 4 weeks, there was a decrease in activation of all caspases, but little further decrease by week 24. T cell mitochondrial membrane potential did not increase until week 12, but continued to increase until week 24. The only predictor of CD4(+) count increase was the increase in mitochondrial membrane potential of naive cells at 6 months (r=0.66, p=0.038). This suggests that positive selection of naive CD4(+) T cells in the thymus is the major determinant of CD4(+) recovery.
    AIDS Research and Human Retroviruses 11/2014; 31(2). DOI:10.1089/aid.2014.0038 · 2.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Monocyte activation during HIV-1 infection is associated with increased plasma levels of inflammatory markers and increased risk for premature development of age-related diseases. Because activated monocytes primarily use glucose to support cellular metabolism, we hypothesized that chronic monocyte activation during HIV-1 infection induces a hypermetabolic response with increased glucose uptake. To test this hypothesis, we evaluated glucose transporter 1 (Glut1) expression and glucose uptake by monocyte subpopulations in HIV-seropositive (HIV(+)) treatment-naive individuals (n = 17), HIV(+) individuals on combination antiretroviral therapy with viral loads below detection (n = 11), and HIV-seronegative (HIV(-)) individuals (n = 16). Surface expression of Glut1 and cellular uptake of the fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose were analyzed by flow cytometry on monocyte subpopulations. Irrespective of treatment status, monocytes from HIV(+) persons had significantly increased surface expression of Glut1 compared with those from HIV(-) controls. Nonclassical (CD14(+)CD16(++)) and intermediate (CD14(++)CD16(+)) monocyte subpopulations showed higher Glut1 expression than did classical (CD14(++)CD16(-)) monocytes. Intermediate monocytes from treatment-naive HIV(+) individuals also showed increased uptake of 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose compared with those from HIV(-) controls. Our results show that HIV infection is associated with increased glucose metabolism in monocytes and that Glut1 expression by proinflammatory monocytes is a potential marker of inflammation in HIV-infected subjects. However, the possibility exists whereby other Gluts such as Glut3 and Glut4 may also support the influx of glucose into activated and inflammatory monocyte populations.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background:Hepatitis C virus (HCV) viremia is thought to have broad systemic effects on the cellular immune system that go beyond its impact on just those T cells that are HCV specific. However, previous studies of chronic HCV and circulating T-cell subsets (activation and differentiation phenotypes) in HIV negatives used general population controls, rather than a risk-appropriate comparison group. Studies in HIV positives did not address overall immune status (total CD4(+) count).Methods:We used fresh blood from HIV-positive and at-risk HIV-negative women, with and without chronic HCV, to measure percentages of activated CD4(+) and CD8(+) T cells, Tregs, and T-cell differentiation phenotypes (naive, central memory, effector memory (EM), and terminally differentiated effector). This included 158 HIV negatives and 464 HIV positives, of whom 18 and 63, respectively, were HCV viremic.Results:In multivariate models of HIV negatives, HCV viremia was associated with 25% fewer naive CD4(+) (P = 0.03), 33% more EM CD4(+) (P = 0.0002), and 37% fewer central memory CD8(+) (P = 0.02) T cells. Among HIV positives, we observed only 1 of these 3 relationships: higher percentage of EM CD4(+) among HCV viremic women. Furthermore, the association with EM CD4(+) among HIV positives was limited to individuals with diminished immune status (total CD4(+) count 500 cells/L), as were associations of HCV viremia with higher percentages of activated CD4(+) and Tregs. Among HIV positives with high CD4(+) count, no significant associations were observed.Conclusions:These data suggest that HCV viremia in HIV negatives is associated with accelerated T-cell differentiation, but among HIV positives, the impact of HCV viremia is less straightforward and varies by total CD4(+) count.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 11/2014; 67(3):295-303. DOI:10.1097/QAI.0000000000000310 · 4.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: HIV IRs and INRs show increased galectin-9 expression on NK and CD4+ T cells.•INRs have less CD16+CD56+ and CD16+CD56− NK cells that express TIM-3 than HIV IRs.•The frequency of TIM-3+CD4+ cells in PBMC is reduced in INRs compared to HIV IRs.•TIM-3 expression on NK and T cells correlates with peripheral CD4 count.
    Clinical Immunology 10/2014; DOI:10.1016/j.clim.2014.10.009 · 3.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alterations in the gut microbiota composition are associated with food allergy. Toll-like receptors (TLR) respond to microbial stimuli. We studied the effects of ligation of TLR on intestinal epithelial cells (IEC) in preventing an allergic effector response. IEC monolayers (T84 cells) were co-cultured with CD3/28-activated PBMC from healthy controls or atopic patients and simultaneously apically exposed to TLR2, TLR4 or TLR9 ligands. The barrier integrity of T84 cell monolayers was significantly reduced upon co-culture with PBMC of food allergic subjects compared to healthy subjects. Apical exposure of IEC to TLR9, ligand prevented PBMC-induced epithelial barrier disruption. Using PBMC from food allergic subjects, apical TLR9 activation on IEC increased the IFN-γ/IL-13 and IL-10/IL-13 ratio, while suppressing pro-inflammatory IL-6, IL-8 and TNF-α production in an IEC-dependent manner. Hence, activation of apical TLR9 on IEC, potentially by microbiota-derived signals, may play an important role in the prevention of allergic inflammation.
    Clinical Immunology 10/2014; DOI:10.1016/j.clim.2014.07.002 · 3.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Older HIV infected subjects were previously found to have significant B cell expansion during initial antiretroviral therapy in a prospective age-differentiated cohort of older and younger (≥45 vs. ≤30 years) HIV-infected subjects initiating antiretroviral therapy (ART) through the AIDS Clinical Trials Group. Here to further describe this expansion, using a subset of subjects from the same cohort, we characterized B cell phenotypes at baseline and after 192 weeks of ART in both older and younger HIV-infected groups and compared them to uninfected age-matched controls. We also examined whether phenotypes at baseline associated with response to tetanus and hepatitis A vaccine at 12 weeks. Forty six subjects were analyzed in the HIV infected group (21 older, 25 younger) and 30 in the control group (15 per age group). We observed naïve B cells to normalize in younger subjects after 192 weeks of ART, while in older subjects naïve B cells increased to greater levels than those of controls (p = 0.045). Absolute resting memory (RM) cell count was significantly lower in the older HIV infected group at baseline compared to controls and numbers normalized after 192 weeks of ART (p<0.001). Baseline RM cell count positively correlated with week 12 increase in antibody to tetanus vaccine among both younger and older HIV-infected subjects combined (p = 0.01), but not in controls. The age-associated naïve B cell expansion is a novel finding and we discuss several possible explanations for this observation. Relationship between RM cells at baseline and tetanus responses may lead to insights about the effects of HIV infection on B cell memory function and vaccine responses.
    PLoS ONE 09/2014; 9(9):e107064. DOI:10.1371/journal.pone.0107064 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective Lactobacillus dominates the lower genital tract microbiota of many women, producing a low vaginal pH, and is important for healthy pregnancy outcomes and protection against several sexually transmitted pathogens. Yet, factors that promote Lactobacillus remain poorly understood. We hypothesized that the amount of free glycogen in the lumen of the lower genital tract is an important determinant of Lactobacillus colonization and a low vaginal pH. Methods Free glycogen in lavage samples was quantified. Pyrosequencing of the 16S rRNA gene was used to identify microbiota from 21 African American women collected over 8–11 years. Results Free glycogen levels varied greatly between women and even in the same woman. Samples with the highest free glycogen had a corresponding median genital pH that was significantly lower (pH 4.4) than those with low glycogen (pH 5.8; p<0.001). The fraction of the microbiota consisting of Lactobacillus was highest in samples with high glycogen versus those with low glycogen (median = 0.97 vs. 0.05, p<0.001). In multivariable analysis, having 1 vs. 0 male sexual partner in the past 6 months was negatively associated, while BMI ≥30 was positively associated with glycogen. High concentrations of glycogen corresponded to higher levels of L. crispatus and L. jensenii, but not L. iners. Conclusion These findings show that free glycogen in genital fluid is associated with a genital microbiota dominated by Lactobacillus, suggesting glycogen is important for maintaining genital health. Treatments aimed at increasing genital free glycogen might impact Lactobacillus colonization.
    PLoS ONE 07/2014; 9(7):e102467. DOI:10.1371/journal.pone.0102467 · 3.53 Impact Factor
  • Hepatology 07/2014; DOI:10.1002/hep.27303 · 11.19 Impact Factor

Publication Stats

14k Citations
2,265.86 Total Impact Points

Institutions

  • 1997–2015
    • Rush University Medical Center
      • Department of Immunology and Microbiology
      Chicago, Illinois, United States
  • 2013–2014
    • Utrecht University
      • Division of Pharmacology
      Utrecht, Utrecht, Netherlands
    • University of California, San Francisco
      • Department of Epidemiology and Biostatistics
      San Francisco, California, United States
  • 2000–2013
    • National Cancer Institute (USA)
      • Experimental Immunology Branch
      베서스다, Maryland, United States
    • Beth Israel Deaconess Medical Center
      • Division of Viral Pathogenesis
      Boston, MA, United States
    • University of North Carolina at Chapel Hill
      North Carolina, United States
  • 2012
    • University of Melbourne
      • Department of Microbiology and Immunology
      Melbourne, Victoria, Australia
  • 1987–2012
    • University of Illinois at Chicago
      • Department of Pediatrics (Peoria)
      Chicago, Illinois, United States
  • 2001–2011
    • CSU Mentor
      Long Beach, California, United States
    • Northwestern Memorial Hospital
      Chicago, Illinois, United States
  • 2010
    • University of California, Davis
      • Division of Infectious and Immunologic Diseases
      Davis, California, United States
  • 1988–2010
    • Rush Medical College
      Chicago, Illinois, United States
  • 2009
    • University of California, Los Angeles
      Los Angeles, California, United States
  • 2007
    • Stanford University
      • Division of Infectious Diseases and Geographic Medicine
      Palo Alto, California, United States
    • Duke University
      Durham, North Carolina, United States
  • 1993–2007
    • Cornell University
      • Department of Molecular Biology
      Итак, New York, United States
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
  • 1999–2006
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2005
    • University of Maryland, Baltimore
      • Institute of Human Virology
      Baltimore, MD, United States
  • 1998–2004
    • Case Western Reserve University
      • Center for AIDS Research
      Cleveland, OH, United States
    • The University of Chicago Medical Center
      • Department of Microbiology and Immunology
      Chicago, Illinois, United States
  • 2003
    • University of Washington Seattle
      • Department of Laboratory Medicine
      Seattle, Washington, United States
    • University of Colorado
      • Division of Infectious Diseases
      Denver, Colorado, United States
  • 1988–2003
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
  • 2002
    • Cook County Hospital
      Chicago, Illinois, United States
    • University of Texas Medical Branch at Galveston
      • Department of Internal Medicine
      Galveston, Texas, United States
    • Texas A&M University - Galveston
      Galveston, Texas, United States
  • 1998–2000
    • Case Western Reserve University School of Medicine
      Cleveland, Ohio, United States
  • 1991–2000
    • National Institutes of Health
      • Branch of Experimental Immunology
      Bethesda, MD, United States
    • Abbott Laboratories
      North Chicago, Illinois, United States
    • University of Wisconsin, Madison
      • Department of Human Oncology
      Madison, MS, United States
  • 1991–1998
    • Northwestern University
      Evanston, Illinois, United States
  • 1990
    • Pennsylvania State University
      • Department of Medicine
      University Park, MD, United States
  • 1989
    • Aurora St. Luke's Medical Center
      Milwaukee, Wisconsin, United States