Role of Sex Hormones in Regulating Innate Immune Protection against HIV in the Human Female Reproductive Tract

2019 ◽  
Vol 15 (1) ◽  
pp. 92-101
Author(s):  
Mickey V. Patel ◽  
Marta Rodríguez-García ◽  
Charles R. Wira
Keyword(s):  
Hiv Infection ◽  
Immune Cells ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Innate Immune ◽  
Hormonal Changes ◽  
Immune Protection ◽  
Stromal Fibroblasts ◽  
Sexually Transmitted ◽  
Adaptive Immune Cells

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.

Antimicrobial peptides in the pathogenesis of infectious complications in obstetrics and gynecology

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
Keyword(s):  
Antimicrobial Peptides ◽  
Reproductive Tract ◽  
Infectious Complications ◽  
Female Reproductive Tract ◽  
Innate Immune ◽  
Cationic Peptides ◽  
Practical Application ◽  
Sexually Transmitted ◽  
Angiogenic Effect

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.

scholarly journals Effects of Tenofovir on Cytokines and Nucleotidases in HIV-1 Target Cells and the Mucosal Tissue Environment in the Female Reproductive Tract

2014 ◽  
Vol 58 (11) ◽  
pp. 6444-6453 ◽  
Author(s):  
Nabanita Biswas ◽  
Marta Rodriguez-Garcia ◽  
Zheng Shen ◽  
Sarah G. Crist ◽  
Jack E. Bodwell ◽  
...  
Keyword(s):  
T Cells ◽  
Biological Activity ◽  
Epithelial Cells ◽  
Hiv Infection ◽  
Proinflammatory Cytokines ◽  
Reproductive Tract ◽  
Biological Activities ◽  
Female Reproductive Tract ◽  
Immune Protection ◽  
Tnf Α

ABSTRACTTenofovir (TFV) is a reverse transcriptase inhibitor used in microbicide preexposure prophylaxis trials to prevent HIV infection. Recognizing that changes in cytokine/chemokine secretion and nucleotidase biological activity can influence female reproductive tract (FRT) immune protection against HIV infection, we tested the hypothesis that TFV regulates immune protection in the FRT. Epithelial cells, fibroblasts, CD4+T cells, and CD14+cells were isolated from the endometrium (Em), endocervix (Cx), and ectocervix (Ecx) following hysterectomy. The levels of proinflammatory cytokines (macrophage inflammatory protein 3α [MIP-3α], interleukin 8 [IL-8], and tumor necrosis factor alpha [TNF-α]), the expression levels of specific nucleotidases, and nucleotidase biological activities were analyzed in the presence or absence of TFV. TFV influenced mRNA and/or protein cytokines and nucleotidases in a cell- and site-specific manner. TFV significantly enhanced IL-8 and TNF-α secretion by epithelial cells from the Em and Ecx but not from the Cx. In contrast, in response to TFV, IL-8 secretion was significantly decreased in Em and Cx fibroblasts but increased with fibroblasts from the Ecx. When incubated with CD4+T cells from the FRT, TFV increased IL-8 (Em and Ecx) and TNF-α (Cx and Ecx) secretion levels. Moreover, when incubated with Em CD14+cells, TFV significantly increased MIP-3α, IL-8, and TNF-α secretion levels relative to those of the controls. In contrast, nucleotidase biological activities were significantly decreased by TFV in epithelial (Cx) and CD4+T cells (Em) but increased in fibroblasts (Em). Our findings indicate that TFV modulates proinflammatory cytokines, nucleotidase gene expression, and nucleotidase biological activity in epithelial cells, fibroblasts, CD4+T cells, and CD14+cells at distinct sites within the FRT.

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
Keyword(s):  
Immune Cells ◽  
Reproductive Tract ◽  
Critical Role ◽  
Female Reproductive Tract ◽  
Type I ◽  
Local Immune Response ◽  
Disease Symptoms ◽  
Sexually Transmitted ◽  
Simplex Virus

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.

scholarly journals Innate immunity and disorders of the female reproductive tract

Reproduction ◽  
2008 ◽  
Vol 135 (6) ◽  
pp. 739-749 ◽  
Author(s):  
Andrew W Horne ◽  
Sarah J Stock ◽  
Anne E King
Keyword(s):  
Immune System ◽  
Ectopic Pregnancy ◽  
Innate Immune System ◽  
Reproductive Tract ◽  
Intrauterine Infection ◽  
Female Reproductive Tract ◽  
Innate Immune ◽  
Normal Female ◽  
Tubal Infertility ◽  
Sexually Transmitted

Sexually transmitted infections, and their associated sequelae, such as tubal infertility, ectopic pregnancy and preterm labour, are a major worldwide health problem. Chlamydia trachomatis infection is thought to be the leading global cause of tubal infertility and tubal ectopic pregnancy. Preterm birth occurs in around 10% of all deliveries, and nearly 30% of preterm deliveries are associated with intrauterine infection. The mucosal innate immune system of the female reproductive tract has evolved to eliminate such sexually transmitted pathogens whilst maintaining its ability to accommodate specialized physiological functions that include menstruation, fertilization, implantation, pregnancy and parturition. The aim of this review was to describe the role and distribution of key mediators of the innate immune system, the natural antimicrobial peptides (secretory leukocyte protease inhibitor, elafin and the defensins) and the pattern recognition toll-like receptors in the normal female reproductive tract and in the context of these pathological processes.

scholarly journals Estradiol modulation of hepatocyte growth factor by stromal fibroblasts in the female reproductive tract

2009 ◽  
Vol 92 (3) ◽  
pp. 1107-1109 ◽  
Author(s):  
Kimberly D. Coleman ◽  
Jacqueline A. Wright ◽  
Mimi Ghosh ◽  
Charles R. Wira ◽  
John V. Fahey
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Stromal Fibroblasts ◽  
Hepatocyte Growth
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