Abstract
Vulvo-vaginal candidiasis (VVC) is a common condition in human immunodeficiency virus (HIV)-infected women. Toll-like receptor (TLR) 2 and TLR4 are key pattern-recognition receptors of the innate immune system in sensing Candida albicans. The aim of this study was to assess the expression of TLR2 and TLR4 signaling pathways in HIV-infected and uninfected women with VVC. Cervico-vaginal fluids (CVF) were obtained from 7 HIV infected and 11 HIV uninfected clinic attendees in KwaZulu-Natal between June, 2011 and December, 2011. VVC was diagnosed clinically and confirmed by Gram stain and culture of genital samples. Monocytes were isolated from a healthy adult volunteer, pre-incubated with anti-TLR2, anti-TLR4 and a combination of anti-TLR2/anti-TLR4 monoclonal antibodies. Monocytes were then stimulated by CVF. Levels of cytokines were measured by Luminex® multiplex immunoassays. Compared with baseline concentrations, stimulation with CVF of HIV+VVC+ women post-TLR2 blockage increased IL-6, IL-10 and IL-13 production by 165.5, 162.5 and 106.7%, respectively. Using paired T-tests, there was a significant difference in the increase of the concentrations of IL-6 (P = 0.04), IL-10 (P = 0.003), and IL-13 (P = 0.031) when comparing stimulation by CVF of HIV+VVC+ versus stimulation by CVF of HIV-VVC+ patients. There was a linear correlation between genital HIV RNA loads and mean level production of IL-6 (r = 0.722; R2 = 0.679; P = 0.067) as well as IL-8 (r = 0.910; R2 = 0.833; P = 0.004). Findings suggest potential roles of TLR2 in the pathogenesis of VVC among HIV-infected women. Key words: Symptomatic VVC, HIV, TLR2 and TLR4.
Highlights
In human immunodeficiency virus (HIV) infected women, symptomatic vulvo-vaginal candidiasis (VVC) is seen to be frequent and less effectively responsive to conventional anti-fungal therapy
The cell wall of C. albicans is composed of pathogen-associated molecular patterns (PAMPs), especially polysaccharides like chitin, 1,3-β-glucans and 1,6-β-glucans and proteins that are heavily mannosylated with mannan side-chains
Studies have shown that TLR2 recognizes phospholipomannans; TLR4 recognizes Olinked mannans and macrophage mannose receptor (MMR) recognizes N-linked mannans (Jouault et al, 2003)
Summary
In human immunodeficiency virus (HIV) infected women, symptomatic vulvo-vaginal candidiasis (VVC) is seen to be frequent and less effectively responsive to conventional anti-fungal therapy. Candida albicans has been reported as the cause of VVC in 85 to 95% of cases (Sobel, 2007). The cell wall of C. albicans is composed of pathogen-associated molecular patterns (PAMPs), especially polysaccharides like chitin, 1,3-β-glucans and 1,6-β-glucans and proteins that are heavily mannosylated with mannan side-chains. Pathogen recognition receptors (PRRs), such as the toll-like receptors (TLRs) and C-type lectins (CLRs) on the surface of antigen presenting cells (APCs) are able to recognize PAMPs. Studies have shown that TLR2 recognizes phospholipomannans; TLR4 recognizes Olinked mannans and macrophage mannose receptor (MMR) recognizes N-linked mannans (Jouault et al, 2003). Whilst the CLR dectin-1 recognizes β-glucan, CLR dectin-2 recognizes mannose residues (McGreal et al, 2006; Brown and Gordon, 2001)
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