AUTHOR=Redondo Natalia , Rodríguez-Goncer Isabel , Parra Patricia , Ruiz-Merlo Tamara , López-Medrano Francisco , González Esther , Polanco Natalia , Trujillo Hernando , Hernández Ana , San Juan Rafael , Andrés Amado , Aguado José María , Fernández-Ruiz Mario 

TITLE=Influence of single-nucleotide polymorphisms in TLR3 (rs3775291) and TLR9 (rs352139) on the risk of CMV infection in kidney transplant recipients

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.929995

DOI=10.3389/fimmu.2022.929995

ISSN=1664-3224

ABSTRACT=<p>Risk stratification for cytomegalovirus (CMV) infection after kidney transplantation (KT) remains to be determined. Since endosomal toll-like receptors (TLRs) are involved in viral sensing, we investigated the impact of common single-nucleotide polymorphisms (SNPs) located within <italic>TLR3</italic> and <italic>TLR9</italic> genes on the occurrence of overall and high-level (≥1,000 IU/ml) CMV infection in a cohort of 197 KT recipients. Homozygous carriers of the minor allele of <italic>TLR3</italic> (rs3775291) had higher infection-free survival compared with reference allele carriers (60.0% for TT versus 42.3% for CC/CT genotypes; <italic>P</italic>-value = 0.050). Decreased infection-free survival was observed with the minor allele of <italic>TLR9</italic> (rs352139) (38.2% for TC/CC versus 59.3% for TT genotypes; <italic>P</italic>-value = 0.004). After multivariable adjustment, the recessive protective effect of the <italic>TLR3</italic> (rs3775291) TT genotype was confirmed (adjusted hazard ratio [aHR]: 0.327; 95% CI: 0.167–0.642; <italic>P</italic>-value = 0.001), as was the dominant risk-conferring effect of <italic>TLR9</italic> (rs352139) TC/CC genotypes (aHR: 1.865; 95% CI: 1.170–2.972; <italic>P</italic>-value = 0.009). Carriers of the <italic>TLR9</italic> (rs352139) TC/CC genotypes showed lower CMV-specific interferon-γ-producing CD4+ T-cell counts measured by intracellular cytokine staining compared with the TT genotype (median of 0.2 versus 0.7 cells/μl; <italic>P</italic>-value = 0.003). In conclusion, <italic>TLR3/TLR9</italic> genotyping may inform CMV infection risk after KT.</p>