scholarly journals Immunoregulatory Functions of Interferons During Genital HSV-2 Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Emily Feng ◽  
Elizabeth Balint ◽  
Fatemah Vahedi ◽  
Ali A. Ashkar

Herpes simplex virus type 2 (HSV-2) infection is one of the most prevalent sexually transmitted infections that disproportionately impacts women worldwide. Currently, there are no vaccines or curative treatments, resulting in life-long infection. The mucosal environment of the female reproductive tract (FRT) is home to a complex array of local immune defenses that must be carefully coordinated to protect against genital HSV-2 infection, while preventing excessive inflammation to prevent disease symptoms. Crucial to the defense against HSV-2 infection in the FRT are three classes of highly related and integrated cytokines, type I, II, and III interferons (IFN). These three classes of cytokines control HSV-2 infection and reduce tissue damage through a combination of directly inhibiting viral replication, as well as regulating the function of resident immune cells. In this review, we will examine how interferons are induced and their critical role in how they shape the local immune response to HSV-2 infection in the FRT.

2019 ◽  
Vol 15 (1) ◽  
pp. 92-101
Author(s):  
Mickey V. Patel ◽  
Marta Rodríguez-García ◽  
Charles R. Wira

Immune protection in the female reproductive tract (FRT) has evolved to meet the challenges of sexually transmitted bacterial and viral pathogens, allogeneic spermatozoa, and an immunologically distinct semi-allogeneic fetus. Throughout the FRT, the innate immune system is essential for the recognition and initial response to incoming pathogens. Key mediators of innate immune protection examined in this review include epithelial cells, stromal fibroblasts, macrophages, DC, and neutrophils from the Fallopian tubes, uterus, cervix and vagina. These innate immune cells respond to pathogens resulting in the secretion of cytokines, chemokines, antimicrobials, and production of intracellular proteins that protect, activate and recruit both innate and adaptive immune cells. Human immunodeficiency virus (HIV) infection can occur throughout the FRT, including the ovary, and is modulated by multiple factors including age of the individual, epithelial barrier integrity, composition of the vaginal microbiome, and hormonal status. Alterations in immune function due to hormonal changes that optimize conditions for successful fertilization create a hypothesized “window of vulnerability” that lasts from ovulation into the secretory stage of the menstrual cycle. The goal of this review is to summarize the multiple levels of protection against HIV infection in the FRT and thereby providing a foundation for the design of vaccines for protection against sexually-transmitted infections (STI) including HIV.


2009 ◽  
Vol 83 (23) ◽  
pp. 12399-12406 ◽  
Author(s):  
Vineet D. Menachery ◽  
David A. Leib

ABSTRACT The type I interferon (IFN) cascade is critical in controlling viral replication and pathogenesis. Recognition pathways triggered by viral infection rapidly induce the type I IFN cascade, often in an IFN regulatory factor 3 (IRF-3)-dependent fashion. This dependence predicts that loss of IRF-3 would render early recognition pathways inoperative and thereby impact virus replication, but this has not been observed previously with herpes simplex virus type 1 (HSV-1) in vitro. In this study, HSV-1-infected IRF-3−/− bone marrow-derived dendritic cells (BMDCs) and macrophages supported increased HSV replication compared to control cells. In addition, IRF-3-deficient BMDCs exhibited delayed type I IFN synthesis compared to control cells. However, while IFN pretreatment of IRF-3−/− BMDCs resulted in reduced virus titers, a far greater reduction was seen after IFN treatment of wild-type cells. This suggests that even in the presence of exogenously supplied IFN, IRF-3−/− BMDCs are inherently defective in the control of HSV-1 replication. Together, these results demonstrate a critical role for IRF-3-mediated pathways in controlling HSV-1 replication in cells of the murine immune system.


2009 ◽  
Vol 3 (1) ◽  
pp. 27-33
Author(s):  
Tahmina Shirin ◽  
Saidur Rahman ◽  
Fareha Jesmin Rabbi ◽  
Md Humayun Kabir ◽  
KZ Mamun

The prevalence of sexually transmitted diseases (STDs) among patients attending out patients department of Skin and Venereal diseases of Dhaka Medical College Hospital, Dhaka and Shahid Sohrawardy Hospital, Dhaka was studied. A total of 230 patients were enrolled in the study during the period of July, 2006 to May, 2007. Urethral and endocervical swabs were collected from the participants for detection of Neisseria gonorrheae (by culture), Chlamydia trachomatis (by immunochromatoghraphy) and blood samples for the detection of Treponema pallidum antibody (by rapid plasma regain and Treponema pallidum haemagglutination assay), Herpes simplex virus type 2 antibody (both IgM and IgG by enzyme linked immunosorbent assay) and Human Immunodeficiency virus antibody (by enzyme linked immunosorbent assay). Socio-demographic data and data regarding high-risk sexual behavior were also collected. Out of 230 participants, 199 (86.5%) were positive for STDs pathogens studied, among them, 98 (42.6%) were infected with single pathogen and 101 (43.9%) were suffering from multiple infections. The prevalences of N. gonorrheae, C. trachomatis, T. pallidum, and HSV type 2 were 90 (39.1%), 110 (47.8%), 28 (12.2%) and 88 (38.2%) respectively. However, none of them were positive for HIV infection. Use of condom was significantly associated with protection of the participants against STDs. Keywords: Sexually Transmitted Diseases, Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Herpes simplex virus type-2, Human Immunodeficiency virus   doi: 10.3329/bjmm.v3i1.2968 Bangladesh J Med Microbiol 2009; 03 (01): 27-33


2019 ◽  
Vol 20 (2) ◽  
pp. 266 ◽  
Author(s):  
Maria Torcia

The vaginal ecosystem is important for women’s health and for a successful reproductive life, and an optimal host-microbial interaction is required for the maintenance of eubiosis. The vaginal microbiota is dominated by Lactobacillus species in the majority of women. Loss of Lactobacillus dominance promotes the colonization by anaerobic bacterial species with an increase in microbial diversity. Vaginal dysbiosis is a very frequent condition which affects the immune homeostasis, inducing a rupture in the epithelial barrier and favoring infection by sexually transmitted pathogens. In this review, we describe the known interactions among immune cells and microbial commensals which govern health or disease status. Particular attention is given to microbiota compositions which, through interplay with immune cells, facilitate the establishment of viral infections, such as Human Immunodeficiency Virus (HIV), Human Papilloma Virus (HPV), Herpes Simplex Virus 2 (HSV2).


2017 ◽  
Vol 35 (06) ◽  
pp. 487-493 ◽  
Author(s):  
Saima Rafique ◽  
James Segars ◽  
Phyllis Leppert

AbstractFibroids (uterine leiomyomas) are the most common benign tumors of the female reproductive tract. Steroid hormones, growth factors, and cytokines have long been implicated in fibroid growth; however, research suggests that changes in the extracellular matrix and mechanical signaling play a critical role in fibroid growth and differentiation. Studies have shown that growth of fibroids is related to the change in the volume and composition of extracellular matrix with increased deposition of abnormal collagen, glycoproteins, laminins, fibronectins, and an increased osmotic stress. These changes generate mechanical stress which is converted to chemical signals in the cells through mechanotransduction and eventually affects gene expression and protein synthesis. Current studies also suggest that mechanical signaling in fibroid cells is abnormal as evidenced by decreased apoptosis of abnormal cells and deposition of a stiff extracellular matrix promoting fibrosis. Understanding and defining these mechanisms could help design new therapies for the treatment of fibroids.


2015 ◽  
Vol 34 (5) ◽  
pp. 279-283 ◽  
Author(s):  
Magidah Kobty

AbstractOne of the most common sexually transmitted infections is the herpes simplex virus (HSV) Type 2. Although the incidence of newborn infection is not as common as in adults, approximately 1,500 neonates are diagnosed annually with HSV infection. HSV can be detrimental to the life of a newborn, with morbidity and mortality rates of up to 65 percent. This article addresses the maternal and fetal complications of HSV and the impact of HSV on the newborn along with diagnostic evaluation methods. In addition, treatment options and evidence-based practices regarding HSV are defined. Despite growing technology and medical treatment for early identification of HSV, this virus remains challenging and can deeply impact the life of an infant and his or her family. Early diagnosis, treatment, and intervention of an infant with HSV are crucial to ensure the livelihood of the newborn.


2014 ◽  
Vol 63 (5) ◽  
pp. 73-81 ◽  
Author(s):  
Olesya Nikolaevna Ivashova ◽  
Olga Petrovna Lebedeva ◽  
Sergey Petrovich Pakhomov ◽  
Natal’ya Alexandrovna Rudyh ◽  
Marina Sergeevna Seliverstova

Antimicrobial peptides (AMP) are cationic peptides of innate immune system with antiviral, antibacterial and antiprotozoal activity. AMP act as immunomodulators, promote bacterial opsonization, inhibit proteases activity, have anti-endotoxic and angiogenic effect. The review describes main types of AMPs, features of their expression in female reproductive tract depending from menstrual cycle and during pregnancy. Data about the role of AMPs in defending from sexually transmitted infections (HIV, genital herpes, HPV, gonorrhea), in pathogenesis of extrauterine pregnancy and preterm birth are described. Possibility of practical application of AMPs as alternative to antibiotics and as contraceptives is estimated.


2015 ◽  
Vol 15 (1) ◽  
pp. 16 ◽  
Author(s):  
Sung Ki Lee ◽  
Chul Jung Kim ◽  
Dong-Jae Kim ◽  
Jee-hyun Kang

2006 ◽  
Vol 74 (10) ◽  
pp. 5773-5779 ◽  
Author(s):  
Raina N. Fichorova ◽  
Radiana T. Trifonova ◽  
Robert O. Gilbert ◽  
Catherine E. Costello ◽  
Gary R. Hayes ◽  
...  

ABSTRACT Trichomonas vaginalis is one of the most common nonviral sexually transmitted human infections and, worldwide, has been linked to increased incidence of human immunodeficiency virus type 1 transmission, preterm delivery, low birth weight, cervical cancer, and vaginitis. The molecular pathways that are important in initiating host inflammatory and immune responses to T. vaginalis are poorly understood. Here we report interactions of human cervicovaginal epithelial cells with the most abundant cell surface glycoconjugate of the parasite, the T. vaginalis lipophosphoglycan (LPG). Purified LPG mediated the adhesion of parasites to human vaginal epithelial cells in a dose-dependent manner. Furthermore, T. vaginalis LPG (but not LPG from Tritrichomonas foetus, the causative agent of bovine trichomoniasis) induced a selective upregulation of chemotactic cytokines by human endocervical, ectocervical, and vaginal epithelial cells, which do not express Toll-like receptor 4/MD2. The T. vaginalis LPG triggered interleukin 8 (IL-8), which promotes the adhesion and transmigration of neutrophils across the endothelium, and macrophage inflammatory protein 3α, which is a chemoattractant for immune cells and is essential for dendritic cell maturation. These effects were dose dependent and sustained in the absence of cytotoxicity and IL-1β release and utilized, at least in part, a signaling pathway independent from the Toll-like/IL-1 receptor adaptor protein MyD88.


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