The Association of TLR2, TLR3, and TLR9 Gene Polymorphisms With Susceptibility to Talaromycosis Among Han Chinese AIDS Patients in Guangdong

Abstract

BackgroundTalaromycosis (TM) caused by Talaromyces marneffei (T. marneffei) is a growing public health concern. Although Toll-like receptor (TLR) genes play a critical role in the host defense against fungal infection, the influence of polymorphisms in these genes on the susceptibility of acquired immune deficiency syndrome (AIDS) patients to TM remains unknown. This study aims to uncover the associations of single nucleotide polymorphisms (SNPs) in TLR genes with TM susceptibility among patients with AIDS.MethodsAltogether 200 AIDS patients complicated with TM, 200 matched AIDS patients without TM, and 76 healthy controls (HCs) were enrolled in this case-control study. In total, 23 SNPs in the TLR2, TLR4, and TLR9 genes, which may influence the susceptibility of AIDS patients to TM, were checked by the time of flight mass spectrometry (TOF/MS) method among these Han Chinese subjects.ResultsNo significant differences in genotype or allele frequencies of selected SNPs were found among the TM group, Non-TM group, and HC group. Haplotype analysis also demonstrated no correlation of these SNPs with TM. However, subgroup analysis showed that the genotype TT and the T allele in TLR2 SNP rs1339 were more frequent in typical TM cases than controls (50.0 vs. 35.8%, 70.5 vs. 59.7%); the frequency of the GT genotype in TLR2 SNP rs7656411 was markedly higher in severe TM cases compared to controls (57.8 vs. 34.4%).ConclusionOur results demonstrate a genetic connection of TLR2 SNPs rs1339 and rs7656411 with an increased susceptibility and severity of TM among Han Chinese populations.

Dynamic m6A profiles reveal the role of YTHDC2‐TLR2 signaling axis in Talaromyces marneffei infection

“…Evidence showed that m 6 A levels on TLR2 mRNA was hypermethylated in TM‐infected cells (Figure 3D), but TLR2 expression was downregulated (Figure 3C). TLR2 is located on the cell surface to detect pathogen invasion, and higher expression levels of TLR2 in macrophages were associated with increased TM cytotoxicity and severity 29,30 . To investigate whether YTHDC2 promotes TM replication by altering m 6 A‐mediated TLR2 expression, we first assess the mRNA levels of TLR2 in YTHDC2 knockdown cells under HIV and/or TM infection, as well as the transcriptional level of cytokine factor (TNF‐α) and chemokine factor (IL1‐β).…”

Talaromyces marneffei Infection: Virulence, Intracellular Lifestyle and Host Defense Mechanisms

“…Recently, an investigation of human genetic polymorphisms was undertaken to predict susceptibility against T. marneffei infection. The approach focused on single nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes of Han Chinese with AIDS demonstrated that SNPs within the TLR2, TLR4, and TLR9 genes may contribute to increasing the susceptibility and severity to T. marneffei [105]. Moreover, the presence of anti-IFN-γ autoantibodies in adult-onset acquired immunodeficiency (AOID) was significantly associated with HLA-DRB1*16:02 and HLA-DQB1*05:02 alleles in these patients [41].…”

Key thermally dimorphic fungal pathogens: shaping host immunity

“…A study using monoclonal antibodies against PRRs on human monocytes to investigate binding to T. marneffei conidia showed that the MR, TLR1, TLR2, TLR4, TLR6, CD14, CD11b and CD18 were all involved in phagocytosis [ 24 ]. Recently, a study in AIDS patients in China linked talaromycosis severity with single-nucleotide polymorphisms in TLR2 but not in TLR3 or TLR9 [ 71 ].…”