Zhong Jinjin, Liu Lulu, Lu Yajie, Gu Yu, Zhao Jiangnan, Chen Bilin, Zhou Wei, Su Xin
Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
J Clin Med. 2022 Mar 28;11(7):1870. doi: 10.3390/jcm11071870.
Non-neutropenic pulmonary aspergillosis is one of the most common and serious fungal infections. Previous studies have shown that single nucleotide polymorphisms (SNPs) of pattern recognition receptors genes are associated with susceptibility to aspergillosis. NOD-like receptors (NLRs) play an important role in the immunological response against fungal infection. In this study, we investigated the relationship between polymorphisms of three NLRs and susceptibility to pulmonary aspergillosis disease in non-neutropenic patients.
We included 73 patients with proven pulmonary aspergillosis and 103 healthy controls. A total of sixteen SNPs in the NLRP3, NLRC4, and NLRC5 genes were detected by PCR-direct sequencing. Then, we evaluated the association between these polymorphisms and susceptibility to aspergillosis.
Fifteen SNPs were consistent with Hardy-Weinberg equilibrium except for NLRP3 rs7525979. A total of eight SNPs (NLRP3 rs3806265, NLRC4 rs212704 and NLRC5 rs1684579, rs12598522, rs3995817, rs3995818, rs34531240, rs28438857) were observed an association with susceptibility of pulmonary aspergillosis. The CC homozygote of NLRP3 rs3806265, TT homozygote of NLRC5 rs1684579 and T allele of NLRC5 rs12598522 were associated with a higher risk of aspergillosis while TT homozygote of NLRC4 rs212704 was associated with a lower risk of aspergillosis. Especially in the invasive pulmonary aspergillosis subgroup, the TT homozygote of NLRC5 rs1684579 and rs3995817, the CC homozygote of NLRC5 rs34531240 and rs28438857, GG homozygote of NLRC5 rs3995818, the C allele and CC homozygote of NLRP3 rs3806265 were associated with higher susceptibility.
This study showed an association between polymorphisms of NLRP3, NLRC4, and NLRC5 and susceptibility to pulmonary aspergillosis for the first time. Further investigations in larger populations are needed, and functional studies are also required to investigate the function of these NLRs in aspergillosis, as well as other fungal infection diseases.
非中性粒细胞减少性肺曲霉病是最常见且严重的真菌感染之一。既往研究表明，模式识别受体基因的单核苷酸多态性（SNP）与曲霉病易感性相关。NOD样受体（NLR）在抗真菌感染的免疫反应中起重要作用。在本研究中，我们调查了3种NLR的多态性与非中性粒细胞减少患者肺曲霉病易感性之间的关系。
我们纳入了73例确诊为肺曲霉病的患者和103名健康对照。通过PCR直接测序检测NLRP3、NLRC4和NLRC5基因中的16个SNP。然后，我们评估了这些多态性与曲霉病易感性之间的关联。
除NLRP3 rs7525979外，15个SNP符合Hardy-Weinberg平衡。共观察到8个SNP（NLRP3 rs3806265、NLRC4 rs212704以及NLRC5 rs1684579、rs12598522、rs3995817、rs3995818、rs34531240、rs28438857）与肺曲霉病易感性相关。NLRP3 rs3806265的CC纯合子、NLRC5 rs1684579的TT纯合子以及NLRC5 rs12598522的T等位基因与曲霉病较高风险相关，而NLRC4 rs212704的TT纯合子与曲霉病较低风险相关。尤其是在侵袭性肺曲霉病亚组中，NLRC5 rs1684579和rs3995817的TT纯合子、NLRC5 rs34531240和rs28438857的CC纯合子、NLRC5 rs3995818的GG纯合子、NLRP3 rs3806265的C等位基因和CC纯合子与较高易感性相关。
本研究首次表明NLRP3、NLRC4和NLRC5的多态性与肺曲霉病易感性之间存在关联。需要在更大人群中进行进一步研究，还需要开展功能研究以探究这些NLR在曲霉病以及其他真菌感染性疾病中的功能。
