HPV Induces Changes in Innate Immune and Adhesion Molecule Markers in Cervical Mucosa With Potential Impact on HIV Infection.

Alan Messala A Britto,Ana Lúcia M Giannini,Marcelo A Soares,Claudia Cicala,Yara Furtado,Cintia Policarpo,Gutemberg Almeida,Aida Sivro,Livia R Goes,Ângela R Meirelles,James Arthos,Elizabeth S Machado

doi:10.3389/fimmu.2020.02078

Abstract

While most HPV infections are asymptomatic and clear spontaneously, persistent infection with high-risk HPVs is associated with cervical cancer and with increased risk of HIV acquisition. Although several hypotheses have been proposed to explain this phenomenon, none has been confirmed. Our aim was to investigate the expression of host factors involved in the susceptibility to HIV infection among HPV-infected women. Cervical samples were collected to characterize the expression levels of HIV susceptibility markers in the mucosa of HPV-infected compared with HPV-uninfected women. No differences in the frequency of CCR5+, integrin α4β7+, activated and memory CD4+ T-cell were detected between the groups. We additionally evaluated the expression levels of genes involved in innate immune responses and in cell adhesion. HPV infected patients expressed higher levels of TLR9 and lower levels of pattern recognition receptors that recognize RNA (TLR3, TLR7, and MDA5/IFIH1). We also detected an impaired IFN pathway, with an increased Type I IFN and a decreased IFNα2 receptor expression. HPV+ samples displayed reduced expression of genes for adherens and tight junctions. Taken together, these results suggest that although HPV infection does not result in the recruitment/activation of susceptible CD4+ T-cell in the female genital tract, it leads to changes in the innate antiviral immune responses and in cell adhesion that are likely to favor HIV infection.

Highlights

Human papillomavirus (HPV) is the agent of a sexually transmitted infection (STI) occurring in ∼12% of the world’s population [1]
A number of studies have documented an association between HPV infection and increased risk of HIV acquisition [7, 9, 34,35,36,37,38], the immune mechanisms that mediate this effect remain largely unexplored
In this study we investigated the underlying mechanism by which HPV increases HIV

Summary

Introduction

Human papillomavirus (HPV) is the agent of a sexually transmitted infection (STI) occurring in ∼12% of the world’s population [1]. In some cases the virus (usually high-risk HPVs— hr-HPV) subverts host defense mechanisms, causing a persistent infection that may lead to premalignant lesions and cancer [2]. It has been shown that immunosuppressive diseases are associated with cervical cancer development [3], and a recent meta-analysis reinforced that HIV-infected women have a higher risk of acquiring HPV [4], potentially due to disruption of tight junctions [5, 6]. HSV2 (herpes simplex virus 2), Haemophilus ducreyi and bacterial vaginosis (BV) cause an increase in the number of CCR5+, activated and α4β7+ integrin CD4+ T-cells in FGT [13,14,15], thereby enhancing HIV susceptibility [12]. Higher number of Tregs, and CD4+ and CD8+ T-cell expressing α4β7 integrin are found in the cervical stroma of women with cervical intraepithelial neoplasia (CIN) lesions, but the presence, quantity and role of these cells in disease pathology is still unclear [16,17,18,19]

Objectives

Methods

Conclusion