Journal
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2021.680665
Keywords
extra-pulmonary TB; helminth infection; matrix metalloproteinases; tissue inhibitors of metalloproteinases; Luminex ELISA
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Funding
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID)
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This study investigated the levels of circulating MMPs and TIMPs in TBL individuals with and without helminth coinfection, revealing that MMPs and TIMPs were elevated in TBL-Hel+ coinfected individuals. Regression analysis showed that these changes were independent of age, sex, and culture status. The MMP-2 ratio with all TIMPs was significantly associated with TBL-helminth coinfection, indicating a profound effect of helminth infection on TBL pathogenesis and immunity.
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 (Strongyloides stercoralis [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 per se. 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.
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