scholarly journals Mucosal Immunity in HIV/SIV Infection: T Cells, B Cells and Beyond

2019 ◽  
Vol 15 (1) ◽  
pp. 63-75 ◽  
Author(s):  
Barbara L. Shacklett
Keyword(s):  
T Cells ◽  
Mucosal Immunity ◽  
Reproductive Tract ◽  
Cell Types ◽  
Female Reproductive Tract ◽  
Multiparameter Flow Cytometry ◽  
Mucosal Tissues ◽  
New Information ◽  
Innate Lymphocytes ◽  
Hiv 1

As our understanding of mucosal immunity increases, it is becoming clear that the host response to HIV-1 is more complex and nuanced than originally believed. The mucosal landscape is populated with a variety of specialized cell types whose functions include combating infectious agents while preserving commensal microbiota, maintaining barrier integrity, and ensuring immune homeostasis. Advances in multiparameter flow cytometry, gene expression analysis and bioinformatics have allowed more detailed characterization of these cell types and their roles in host defense than was previously possible. This review provides an overview of existing literature on immunity to HIV-1 and SIVmac in mucosal tissues of the female reproductive tract and the gastrointestinal tract, focusing on major effector cell populations and briefly summarizing new information on tissue-resident memory T cells, Treg, Th17, Th22 and innate lymphocytes (ILC), subsets that have been studied primarily in the gastrointestinal mucosa.

scholarly journals Complement Receptor 3 Mediates HIV-1 Transcytosis across an Intact Cervical Epithelial Cell Barrier: New Insight into HIV Transmission in Women

mBio ◽  
2022 ◽  
Author(s):  
Christopher J. Day ◽  
Rachael L. Hardison ◽  
Belinda L. Spillings ◽  
Jessica Poole ◽  
Joseph A. Jurcisek ◽  
...  
Keyword(s):  
T Cells ◽  
Epithelial Cell ◽  
Reproductive Tract ◽  
Hiv Transmission ◽  
Primary Site ◽  
Female Reproductive Tract ◽  
Complement Receptor ◽  
Complement Receptor 3 ◽  
Insight Into ◽  
Hiv 1

In women, the lower female reproductive tract is the primary site for HIV infection. How HIV traverses the epithelium to infect CD4 T cells in the submucosa is ill-defined.

scholarly journals Human Mucosal Mast Cells Capture HIV-1 and Mediate Viraltrans-Infection of CD4+T Cells

2015 ◽  
Vol 90 (6) ◽  
pp. 2928-2937 ◽  
Author(s):  
Ai-Ping Jiang ◽  
Jin-Feng Jiang ◽  
Ji-Fu Wei ◽  
Ming-Gao Guo ◽  
Yan Qin ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cells ◽  
Cell Surface ◽  
Bacterial Infections ◽  
Mucosal Mast Cells ◽  
Mucosal Tissues ◽  
Viral Particles ◽  
Molecular Patterns ◽  
Hiv 1

ABSTRACTThe gastrointestinal mucosa is the primary site where human immunodeficiency virus type 1 (HIV-1) invades, amplifies, and becomes persistently established, and cell-to-cell transmission of HIV-1 plays a pivotal role in mucosal viral dissemination. Mast cells are widely distributed in the gastrointestinal tract and are early targets for invasive pathogens, and they have been shown to have increased density in the genital mucosa in HIV-infected women. Intestinal mast cells express numerous pathogen-associated molecular patterns (PAMPs) and have been shown to combat various viral, parasitic, and bacterial infections. However, the role of mast cells in HIV-1 infection is poorly defined. In this study, we investigated their potential contributions to HIV-1 transmission. Mast cells isolated from gut mucosal tissues were found to express a variety of HIV-1 attachment factors (HAFs), such as DC-SIGN, heparan sulfate proteoglycan (HSPG), and α4β7 integrin, which mediate capture of HIV-1 on the cell surface. Intriguingly, following coculture with CD4+T cells, mast cell surface-bound viruses were efficiently transferred to target T cells. Prior blocking with anti-HAF antibody or mannan before coculture impaired viraltrans-infection. Cell-cell conjunctions formed between mast cells and T cells, to which viral particles were recruited, and these were required for efficient cell-to-cell HIV-1 transmission. Our results reveal a potential function of gut mucosal mast cells in HIV-1 dissemination in tissues. Strategies aimed at preventing viral capture and transfer mediated by mast cells could be beneficial in combating primary HIV-1 infection.IMPORTANCEIn this study, we demonstrate the role of human mast cells isolated from mucosal tissues in mediating HIV-1trans-infection of CD4+T cells. This finding facilitates our understanding of HIV-1 mucosal infection and will benefit the development of strategies to combat primary HIV-1 dissemination.

HIV-1 infection of the female reproductive tract

2005 ◽  
Vol 2 (1) ◽  
pp. 35-38 ◽  
Author(s):  
Alexandra L. Howell ◽  
Susana N. Asin ◽  
Grant R. Yeaman ◽  
Charles R. Wira
Keyword(s):  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Hiv 1

scholarly journals Selection following isolation of human immunodeficiency virus type 1 in peripheral blood mononuclear cells and herpesvirus saimiri-transformed T cells is comparable

2002 ◽  
Vol 83 (6) ◽  
pp. 1343-1352 ◽  
Author(s):  
Natalie N. Zheng ◽  
Cherelyn Vella ◽  
Philippa J. Easterbrook ◽  
Rod S. Daniels
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Mononuclear Cells ◽  
Cell Types ◽  
Herpesvirus Saimiri ◽  
Peripheral Blood Mononuclear ◽  
Immunodeficiency Virus ◽  
Blood Mononuclear Cells ◽  
Hiv 1

In attempts to improve isolation rates and virus yields for human immunodeficiency virus (HIV), the use of herpesvirus saimiri-immortalized T cells (HVS T cells) has been investigated as an alternative to/improvement over peripheral blood mononuclear cells (PBMCs). Here we characterize isolates rescued, in the two cell types, from two asymptomatic, long-term non-progressing HIV-1-infected individuals. All rescued viruses replicated in PBMCs and HVS T cells only, displaying a non-syncytium inducing (NSI) phenotype, and using CCR5 as co-receptor. Furthemore, PBMC/HVS T cell virus pairs displayed similar neutralization profiles. Full-length, expression-competent env genes were rescued from all virus isolates and directly from the patient samples using proviral DNA and viral RNA as templates. Compared with the sequences retrieved directly from the patient samples, both cell types showed similar selection characteristics. Whilst the selections were distinct for individual patient samples, they shared a common characteristic in selecting for viruses with increased negative charge across the V2 domain of the viral glycoproteins. The latter was observed at the env gene sequencing level for three other patients whose HIV strains were isolated in PBMCs only. This further supports a common selection for viral sequences that display a macrophage-tropic/NSI phenotype and shows that HVS T cells are a viable alternative to PBMCs for HIV-1 isolation.

scholarly journals Intron-containing RNA from the HIV-1 provirus activates type I interferon and inflammatory cytokines

2017 ◽  
Author(s):  
Sean Matthew McCauley ◽  
Kyusik Kim ◽  
Anetta Nowosielska ◽  
Ann Dauphin ◽  
Leonid Yurkovetskiy ◽  
...  
Keyword(s):  
T Cells ◽  
Antiviral Therapy ◽  
Antiviral Drug ◽  
Cell Types ◽  
Innate Immune ◽  
Type I ◽  
Infected People ◽  
Innate Immune Signaling ◽  
Post Transcriptional Regulation ◽  
Hiv 1

ABSTRACTHIV-1-infected people who take drugs that suppress viremia to undetectable levels are protected from developing AIDS. Nonetheless, these individuals have chronic inflammation associated with heightened risk of cardiovascular pathology. HIV-1 establishes proviruses in long-lived CD4+memory T cells, and perhaps other cell types, that preclude elimination of the virus even after years of continuous antiviral therapy. Though the majority of proviruses that persist during antiviral therapy are defective for production of infectious virions, many are expressed, raising the possibility that the HIV-1provirus or its transcripts contribute to ongoing inflammation. Here we found that the HIV-1 provirus activated innate immune signaling in isolated dendritic cells, macrophages, and CD4+T cells. Immune activation required transcription from the HIV-1 provirus and expression of CRM1-dependent, Rev-dependent, RRE-containing, unspliced HIV-1 RNA. Ifrevwas providedin trans, all HIV-1 coding sequences were dispensable for activation except thosecis-acting sequences required for replication or splicing. These results indicate that the complex, post-transcriptional regulation intrinsic to HIV-1 RNA is detected by the innate immune system as a danger signal, and that drugs which disrupt HIV-1 transcription or HIV-1 RNA metabolism would add qualitative benefit to current antiviral drug regimens.

Development of parthenogenetic and fertilized mouse embryos in the uterus and in extra-uterine sites

Development ◽  
1975 ◽  
Vol 34 (2) ◽  
pp. 387-405
Author(s):  
S. A. Iles ◽  
M. W. McBurney ◽  
S. R. Bramwell ◽  
Z. A. Deussen ◽  
C. F. Graham
Keyword(s):  
Reproductive Tract ◽  
Neural Tissue ◽  
Cell Types ◽  
Mouse Embryos ◽  
Female Reproductive Tract ◽  
Embryonic Cells ◽  
Haploid Embryos ◽  
Keratinized Epithelium ◽  
Mouse Eggs

Mouse eggs were activated with hyaluronidase in vitro and subsequently transferred to the oviduct. In the female reproductive tract they formed morulae and blastocysts which died soon after implantation. Haploid blastocysts were transferred beneath the kidney capsule and here some formed disorganized egg-cylinder structures in a week. Morulae and blastocysts from haploid and diploid parthenogenones were also transferred beneath the testis capsule. Two to four months later the growths which had formed were sectioned. They contained neural tissue, pigment, keratinized epithelium, glandular epithelium, ciliated epithelium, cartilage, bone, muscle, adipose tissue, and haemopoietic tissue. The range of cell types was similar to that produced by fertilized control blastocysts except that the parthenogenones did not form identifiable yolk-sac carcinoma or embryonal carcinomacells. The growths from haploid and diploid parthenogenones in the testis were stained with Feulgen and their DNA content measured. Growths from diploid embryos contained the normal diploid amount of DNA while growths from haploid embryos contained less than this amount. Cell cultures were prepared from the growths. The cells which were investigated contained no Y chromosome, suggesting that they were derived from the embryonic cells rather than the cells of the male host. These cells contained a near diploid chromosome number, although some of them were originally derived from haploid embryos.

Wnt-7a maintains appropriate uterine patterning during the development of the mouse female reproductive tract

Development ◽  
1998 ◽  
Vol 125 (16) ◽  
pp. 3201-3211 ◽  
Author(s):  
C. Miller ◽  
D.A. Sassoon
Keyword(s):  
Reproductive Tract ◽  
Hox Genes ◽  
Cell Types ◽  
Female Reproductive Tract ◽  
Molecular Characteristics ◽  
Anteroposterior Patterning ◽  
Stratified Epithelium ◽  
Distinct Cell ◽  
Hoxa Gene Expression ◽  
Posterior Shift

The murine female reproductive tract differentiates along the anteroposterior axis during postnatal development. This process is marked by the emergence of distinct cell types in the oviduct, uterus, cervix and vagina and is dependent upon specific mesenchymal-epithelial interactions as demonstrated by earlier heterografting experiments. Members of the Wnt family of signaling molecules have been recently identified in this system and an early functional role in reproductive tract development has been demonstrated. Mice were generated using ES-mediated homologous recombination for the Wnt-7a gene (Parr, B. A. and McMahon, A. P. (1995) Nature 374, 350–353). Since Wnt-7a is expressed in the female reproductive tract, we examined the developmental consequences of lack of Wnt-7a in the female reproductive tract. We observe that the oviduct lacks a clear demarcation from the anterior uterus, and acquires several cellular and molecular characteristics of the uterine horn. The uterus acquires cellular and molecular characteristics that represent an intermediate state between normal uterus and vagina. Normal vaginas have stratified epithelium and normal uteri have simple columnar epithelium, however, mutant uteri have stratified epithelium. Additionally, Wnt-7a mutant uteri do not form glands. The changes observed in the oviduct and uterus are accompanied by a postnatal loss of hoxa-10 and hoxa-11 expression, revealing that Wnt-7a is not required for early hoxa gene expression, but is required for maintenance of expression. These clustered hox genes have been shown to play a role in anteroposterior patterning in the female reproductive tract. In addition to this global posterior shift in the female reproductive tract, we note that the uterine smooth muscle is disorganized, indicating development along the radial axis is affected. Changes in the boundaries and levels of other Wnt genes are detectable at birth, prior to changes in morphologies. These results suggest that a mechanism whereby Wnt-7a signaling from the epithelium maintains the molecular and morphological boundaries of distinct cellular populations along the anteroposterior and radial axes of the female reproductive tract.

scholarly journals Vitamin D Status Impacts Genital Mucosal Immunity and Markers of HIV-1 Susceptibility in Women

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3176
Author(s):  
Sharon M. Anderson ◽  
Andrea R. Thurman ◽  
Neelima Chandra ◽  
Suzanne S. Jackson ◽  
Susana Asin ◽  
...  
Keyword(s):  
Vitamin D ◽  
Reproductive Tract ◽  
Serum Vitamin ◽  
Female Reproductive Tract ◽  
High Dose ◽  
Vitamin D Status ◽  
Serum Vitamin D ◽  
Vitamin D Levels ◽  
Hiv 1

While vitamin D insufficiency is known to impact a multitude of health outcomes, including HIV-1, little is known about the role of vitamin D-mediated immune regulation in the female reproductive tract (FRT). We performed a pilot clinical study of 20 women with circulating 25(OH)D levels <62.5 nmol/L. Participants were randomized into either weekly or daily high-dose oral vitamin D supplementation groups. In addition to serum vitamin D levels, genital mucosal endpoints, including soluble mediators, immune cell populations, gene expression, and ex vivo HIV-1 infection, were assessed. While systemic vitamin D levels showed a significant increase following supplementation, these changes translated into modest effects on the cervicovaginal factors studied. Paradoxically, post-supplementation vitamin D levels were decreased in cervicovaginal fluids. Given the strong correlation between vitamin D status and HIV-1 infection and the widespread nature of vitamin D deficiency, further understanding of the role of vitamin D immunoregulation in the female reproductive tract is important.

scholarly journals CCR5, CXCR4, and CD4 Are Clustered and Closely Apposed on Microvilli of Human Macrophages and T Cells

2001 ◽  
Vol 75 (8) ◽  
pp. 3779-3790 ◽  
Author(s):  
Irwin I. Singer ◽  
Solomon Scott ◽  
Douglas W. Kawka ◽  
Jayne Chin ◽  
Bruce L. Daugherty ◽  
...  
Keyword(s):  
T Cells ◽  
Chemokine Receptors ◽  
Inflammatory Responses ◽  
Cell Types ◽  
Cellular Membrane ◽  
Major Elements ◽  
Cellular Migration ◽  
Directional Information ◽  
Virus Adsorption ◽  
Hiv 1

ABSTRACT The chemokine receptors CCR5 and CXCR4 act synergistically with CD4 in an ordered multistep mechanism to allow the binding and entry of human immunodeficiency virus type 1 (HIV-1). The efficiency of such a coordinated mechanism depends on the spatial distribution of the participating molecules on the cell surface. Immunoelectron microscopy was performed to address the subcellular localization of the chemokine receptors and CD4 at high resolution. Cells were fixed, cryoprocessed, and frozen; 80-nm cryosections were double labeled with combinations of CCR5, CXCR4, and CD4 antibodies and then stained with immunogold. Surprisingly, CCR5, CXCR4, and CD4 were found predominantly on microvilli and appeared to form homogeneous microclusters in all cell types examined, including macrophages and T cells. Further, while mixed microclusters were not observed, homogeneous microclusters of CD4 and the chemokine receptors were frequently separated by distances less than the diameter of an HIV-1 virion. Such distributions are likely to facilitate cooperative interactions with HIV-1 during virus adsorption to and penetration of human leukocytes and have significant implications for development of therapeutically useful inhibitors of the entry process. Although the mechanism underlying clustering is not understood, clusters were observed in small trans-Golgi vesicles, implying that they were organized shortly after synthesis and well before insertion into the cellular membrane. Chemokine receptors normally act as sensors, detecting concentration gradients of their ligands and thus providing directional information for cellular migration during both normal homeostasis and inflammatory responses. Localization of these sensors on the microvilli should enable more precise monitoring of their environment, improving efficiency of the chemotactic process. Moreover, since selectins, some integrins, and actin are also located on or in the microvillus, this organelle has many of the major elements required for chemotaxis.

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