Impaired PRR expression modulates inflammation-triggered oxidative stress and pathogenesis of recurrent vulvovaginal infections

Namarta Kalia,Manpreet Kaur,Sujata Sharma,Jatinder Singh

doi:10.1186/s42269-019-0147-1

Abstract

IntroductionBoth inflammation and oxidative stress (OS) stimulate each other and act together in providing defense against recurrent vulvovaginal infections (RVVI). Both processes are in such a tight link, that defect in one may lead to defect in other; therefore, recognition and treatment of primary anomaly are of great clinical importance.ObjectiveTo investigate the relationship between PRRs, i.e., mannose-binding lectin (MBL) and dendritic cell-associated C-type lectin-1 (Dectin-1) and oxidative stress parameters, i.e., total antioxidant status (TAC), total oxidant status (TOS), and oxidative stress index (OSI), along with their dependency on system factors in modulating susceptibility to RVVI.Study designThis case-control study included 258 RVVI cases and 203 age-matched controls. TAC, TOS, and OSI were determined according to modified standard protocols. MBL and Dectin-1 levels were assessed by commercially available kits.ResultsRVVI and bacterial vaginosis showed significantly low TAC than controls. Significantly low TOS was observed in cases than controls. RVVI and vulvovaginal candidiasis showed significantly low OSI than controls. Significantly low MBL and high Dectin-1 levels were observed in cases than controls. Significant, but unexpected weak relationship, was observed between OS parameters and PRRs. Serum biomarkers were found to be dependent on confounding variables.ConclusionLow MBL levels were found to be the primary source of defect in the present study that leads to the dysregulated immune system with no observed protective oxidative stress, increasing susceptibility to RVVI. Therefore, substituting the required MBL in representative Indian population may restore host homeostasis and provide recovery from RVVI.

Highlights

Both inflammation and oxidative stress (OS) stimulate each other and act together in providing defense against recurrent vulvovaginal infections (RVVI)
Low mannose-binding lectin (MBL) levels were found to be the primary source of defect in the present study that leads to the dysregulated immune system with no observed protective oxidative stress, increasing susceptibility to RVVI
This further suggests the importance to take into account the dependency of serum biomarkers on exogenous factors before considering these parameters as potential risk markers of RVVI. In conclusion, both inflammation and oxidative stress stimulate each other and act together in providing defense against RVVI. Both processes are in such a tight link, that defect in one may lead to defect in other, contributing to the pathogenesis of RVVI

Summary

Introduction

Both inflammation and oxidative stress (OS) stimulate each other and act together in providing defense against recurrent vulvovaginal infections (RVVI). Inflammation is a fine mechanism of host immune system that is meant to eliminate pathogens This process involves pattern recognition receptors (PRRs) activation by pathogen-associated molecular patterns (PAMPs) that further induce downstream signaling pathways and subsequent release of inflammatory immune mediators, with the aim of pathogens killing by effector phagocytic cells (Medzhitov, 2008). All these inflammatory stages generate reactive oxidants as an essential part of defense mechanism, leading to a state of oxidative stress (Lugrin et al, 2014). The NOS exist in three different isoforms, in which neuronal NOS (nNOS) and endothelial NOS (eNOS) express constitutively, while inducible NOS (iNOS) express only upon stimulation by pathogen, PAMPs. and by pro-inflammatory cytokines (Förstermann & Sessa, 2011)

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