National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
National Institute for Research in Tuberculosis (NIRT), Chennai, India.
Front Cell Infect Microbiol. 2021 Jul 19;11:680665. doi: 10.3389/fcimb.2021.680665. eCollection 2021.
Matrix metalloproteinases (MMPs) are crucial for tissue remodeling and repair and are expressed in diverse infections, whereas tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of MMPs. However, the interaction of MMPs and TIMPs in tuberculous lymphadenitis (TBL), an extra-pulmonary form of tuberculosis (EPTB) and helminth (Hel+) coinfection is not known. Therefore, this present study investigates the levels of circulating MMPs (1, 2, 3, 7, 8, 9, 12, 13) and TIMPs (1, 2, 3, 4) in TBL individuals with helminth ( [Ss], hereafter Hel+) coinfection and without helminth coinfection (hereafter, Hel-). In addition, we have also carried out the regression analysis and calculated the MMP/TIMP ratios between the two study groups. We describe that the circulating levels of MMPs (except MMP-8 and MMP-12) were elevated in TBL-Hel+ coinfected individuals compared to TBL-Hel- individuals. Similarly, the systemic levels of TIMPs (1, 2, 3, 4) were increased in TBL-Hel+ compared to TBL-Hel- groups indicating that it is a feature of helminth coinfection . Finally, our multivariate analysis data also revealed that the changes in MMPs and TIMPs were independent of age, sex, and culture status between TBL-Hel+ and TBL-Hel- individuals. We show that the MMP-2 ratio with all TIMPs were significantly associated with TBL-helminth coinfection. Thus, our results describe how helminth infection has a profound effect on the pathogenesis of TBL and that both MMPs and TIMPs could dampen the immunity against the TBL-Hel+ coinfected individuals.
基质金属蛋白酶(MMPs)对于组织重塑和修复至关重要,并且在各种感染中表达,而金属蛋白酶抑制剂(TIMPs)是 MMPs 的内源性抑制剂。然而,MMPs 和 TIMPs 在结核性淋巴结炎(TBL)中的相互作用,TBL 是肺结核(EPTB)的一种肺外形式,并且与寄生虫(Hel+)共感染,目前还不清楚。因此,本研究调查了循环 MMPs(1、2、3、7、8、9、12、13)和 TIMPs(1、2、3、4)在 TBL 个体中与寄生虫([Ss],以下简称 Hel+)共感染和无寄生虫共感染(以下简称 Hel-)的水平。此外,我们还进行了回归分析,并计算了两组研究之间的 MMP/TIMP 比值。我们描述了在 TBL-Hel+共感染个体中,除 MMP-8 和 MMP-12 外,循环 MMPs 水平升高。同样,与 TBL-Hel-组相比,TBL-Hel+组中系统性 TIMPs(1、2、3、4)水平升高,表明寄生虫共感染是一个特征。最后,我们的多变量分析数据还表明,MMPs 和 TIMPs 的变化独立于 TBL-Hel+和 TBL-Hel-个体之间的年龄、性别和培养状态。我们发现 MMP-2 与所有 TIMPs 的比值与 TBL-寄生虫共感染显著相关。因此,我们的结果表明寄生虫感染如何对 TBL 的发病机制产生深远影响,并且 MMPs 和 TIMPs 都可能抑制对 TBL-Hel+共感染个体的免疫力。