Diagnostics to Pathogenomics of Sexually Transmitted Infections

Sunit Kumar Singh

• Publisher: Wiley-Blackwell
• Year: 2018
• ISBN:
  9781119380955
• Edition: 1
• Topic: Sciences biologiques
• Subtopic: Microbiologie

Comprehensively explores sexually transmitted diseases, from epidemiology, causative pathogens, clinical impact, and immunology, to management strategies utilizing new strategies of genomics and next-generation diagnostic tools

Sexually transmitted infections (STI) are very common worldwide. More than 20 different STIs have been identified, and about 19 million men and women are infected each year in the United States alone. This book looks at the complete picture of common STIs— how they form, evolve, and transmit, as well as how they can be treated and managed with modern techniques, medicines, and tools.

Diagnostics to Pathogenomics of Sexually Transmitted Infections runs the spectrum of discussion ranging from introduction of causative pathogen, their pathogenesis to epidemiology, immunology, to anatomy and physiology of human genitalia and management strategies. The book offers in-depth chapter coverage on effect of probiotics on reproductive health; mucosal immunity in sexually transmitted infections; the role of circumcision in preventing STIs; Human Immunodeficiency Virus (HIV); genital herpes; molluscum contagiosum; genital warts; chlaymydia trachomatis; donovanosis; gonorrhoea; treponematoses; genital mycoplasms; bacterial vaginosis; vulvovaginal candidiasis; chlaymydia; scabies; chancroid, yeast infections; and more.

• Comprehensively compiles most of the major sexually transmitted infections
• Presents updated information on clinical aspects of sexually transmitted infections
• Examines the priorities in pathogenesis of human sexually transmitted infections and discusses new strategies of genomics and next-generation diagnostic tools used for detection of such pathogens
• Explores the future of rapid molecular diagnostic techniques and the challenges posed in the diagnosis of human STIs
• Includes bench to bedside content that will appeal to both basic and clinical researchers

By offering the latest knowledge about recent advances in sexually transmitted infections in an interdisciplinary fashion, Diagnostics to Pathogenomics of Sexually Transmitted Infections is the perfect book for virologists, microbiologists, infectious disease experts, vaccinologists, biomedical researchers, clinicians, pharmacologists, and public health specialists.

1
Mucosal Immunity in Sexually Transmitted Infections

Jiri Mestecky^1,2 and Michael W. Russell³

¹ Department of Microbiology, University of Alabama at Birmingham, Birmingham, Al, USA

² Institute of Immunology and Microbiology, First School of Medicine, Charles University, Prague, Czech Republic

³ Department of Microbiology and Immunology, University of Buffalo, Buffalo, NY, USA

1.1 Introduction

Quantitative evaluation of the cells involved in the immune system, such as lymphocytes, plasma cells, macrophages, dendritic cells, and epithelial cells, together with their products, including antibodies, cytokines, and humoral factors of innate immunity, convincingly revealed that the immune system associated with the mucosae is greater than its systemic counterpart (Russell et al. 2015a). This fact should not be surprising, as the development of the entire immune system during evolution and continuously in everyday life is driven by stimulation with commensal microbiota, antigens present in food and inhaled air, as well as pathogens throughout the enormous surface area of mucosal sites, which far exceeds the skin surface.

The mucosal immune system comprises anatomically remote and physiologically distinct compartments that provide protection at various mucosal sites. Although the genital tract shares some common features with other mucosae, including the presence of humoral factors and cells of innate immunity, and the origin of cells involved in antibody production and T cell‐mediated immunity, there are also many distinct features characteristic of the genital tract (Russell and Mestecky 2002, 2010; Mestecky et al. 2005). The spectrum of antigens including commensal or pathogenic microorganisms, and sperm is different from those at other mucosal sites. Furthermore, the primary physiological role of the genital tract is reproduction, which involves the acceptance of allogeneic sperm and semi‐allogeneic offspring. This distinct physiological role influences the immune system of the genital tract with respect to the induction or suppression of immune responses, which must be considered in the development and application of vaccines against infectious agents of sexually transmitted diseases.

1.2 Innate Immunity in the Genital Tract

Like other mucosal tracts, the genital tract is rich in cellular and humoral components of innate immunity, but the contributions of these disparate factors to defense against sexually transmitted infections (STI) is not well understood. Typically, more information is available for the female than for the male tract. Distinction must be made at the outset between humoral antimicrobial defense factors, usually proteins of diverse nature and mode of action, and nonspecific factors such as pattern recognition receptors and cytokines that orchestrate the inflammatory and adaptive immune responses, and that recruit, activate, and induce both cellular and molecular defense mechanisms.

1.2.1 Humoral Defense Factors in Female Secretions

Secretions of the male and female genital tracts contain an array of innate antimicrobial defense factors similar to those found in other, often better studied secretions, such as milk, saliva, and intestinal and respiratory secretions. These include lactoferrin, lysozyme, peroxidase, defensins, and other proteins secreted by epithelial cells (Hajishengallis and Russell 2015; Ouellette 2015) (Table 1.1). While many of these are constitutively produced, some are upregulated or induced by cytokines, such as IL‐17 and IL‐22 generated by Th17 cells or by innate lymphoid cells, especially those designated as ILC3. However, there is relatively little information on the role these factors play in defense of the genital tract against STI pathogens. On the other hand, it may be argued that the presence of these factors sets the minimum requirements for the colonization of mucosal surfaces, as organisms that cannot adapt to the conditions created by these factors would be unable to establish themselves as either commensals or pathogens.

Table 1.1 Some Innate Defense Factors Found in the Human Genital Tract.

Factor	Female	Male
Lactoferrin	1 μg ml^−1 (vaginal fluid)	1.2 mg ml^−1 (semen)
	0.1 mg ml^−1 (cervical mucus plug)	Identified by IHC^a in urethral epithelial cells
Lysozyme	13 μg ml^−1 (vaginal fluid)	Identified by IHC in glands of Littré and intra‐epithelial cells
	1 mg ml^−1 (cervical mucus plug)
Peroxidase	Identified in vaginal fluid
Defensins	HD‐5 and HBD‐1 found in cervicovaginal secretions, endocervical and endometrial cells	HD‐5 present in urethral secretions as proHD‐5, activated by proteases
SLPI^b	Produced in glandular epithelium	Identified by IHC in urethral epithelial cells
MBL^c	Found in cervicovaginal lavage	1–25 ng ml^−1 (semen)

^aImmunohistochemical staining.

^bSecretory leukocyte protease inhibitor.

^cMannose‐binding lectin.

In addition, female genital secretions contain abundant mucus, which can form a physical plug at the cervix, and at ovulation under the influence of estrogen, this liquefies to facilitate passage of sperm. The vaginal environment is normally acidic, maintained largely by the dominant presence of Lactobacillus sp., and an increase in pH is associated with dysbiosis that can result in bacterial vaginosis (Russell et al. 2005).

Lactoferrin is a non‐heme iron‐binding protein (M_r ~80 000) related to serum transferrin, but found in most external secretions (reviewed in Hajishengallis and Russell 2015). In the presence of bicarbonate ion, it binds Fe³⁺ with extremely high affinity even at acidic pH down to pH 3. This effectively keeps the secretions in a free'iron‐depleted state, which means that both commensal and pathogenic bacteria colonizing mucosal surfaces must develop alternative mechanisms for obtaining this essential element. Bacteria also use iron‐sensing mechanisms to detect when they are located within animal systems, and respond by activating a wide variety of genes involved not only in iron acquisition but also in adapting to the in vivo environment. Approximately half of all gonococcal isolates express lactoferrin‐binding proteins, LbpA and LbpB, through which they can extract iron from human lactoferrin (Anderson et al. 2003). However, strains that...

Table of contents

• Cover
• Table of Contents
• About the Editor – Prof. Sunit K. Singh
• Preface
• 1 Mucosal Immunity in Sexually Transmitted Infections
• 2 The Role of Circumcision in Preventing Sexually Transmitted Infections
• 3 Effect of Probiotics on Reproductive Health
• 4 Human Immunodeficiency Virus (HIV) Infection
• 5 Genital Herpes
• 6 Molluscum Contagiosum
• 7 Genital Warts
• 8 Chlamydia Trachomatis Urogenital Infections: Epidemiology, Clinical Presentations, and Pathogenesis
• 9 Donovanosis
• 10 Gonorrhea
• 11 Sexually Transmitted Treponematoses
• 12 Genital Mycoplasmas
• 13 Bacterial Vaginosis
• 14 Chancroid
• 15 Vulvovaginal Candidosis
• 16 Tinea Cruris
• 17 Trichomonas Vaginalis
• 18 Scabies
• Index
• End User License Agreement