Interplay of DDP4 and IP-10 as a Potential Mechanism for Cell Recruitment to Tuberculosis Lesions

Frontiers in Immunology
Thomas BlauenfeldtMorten Ruhwald

Abstract

Mycobacterium tuberculosis is one of the world's most successful pathogens equipped to establish itself within the human host as a subclinical infection without overt disease. Unable to eradicate the bacteria, the immune system contains the infection in a granuloma structure. Th1 cells that are essential for infection control are recruited to the site of infection directed by chemokines, predominantly CXCL10. It has previously been shown that CXCL10 in the plasma of patients chronically infected with hepatitis C virus is present primarily in an antagonist form. This is due to N-terminal truncation by the enzyme DPP4, which results in the antagonist form that is capable of binding its receptor CXCR3, but does not induce signaling. We aimed to explore whether such CXCL10 antagonism may have an impact on the pathogenesis of tuberculosis (TB). We measured plasma levels of agonist and antagonist CXCL10 by Simoa digital ELISA, as well as DPP4 enzyme activity in the plasma of 20 patients with active TB infection, 10 patients with pneumonia infection, and a group of 10 healthy controls. We found higher levels of total and antagonist CXCL10 and reduced DPP4 enzyme activity in the plasma of TB patients compared to controls. We traced the...Continue Reading

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Citations

Jan 29, 2020·The Journal of Biological Chemistry·David Diaz-JimenezJohn A Cidlowski
Oct 23, 2019·Frontiers in Cellular and Infection Microbiology·Cristian Alfredo Segura-CerdaMario Alberto Flores-Valdez
Dec 10, 2019·The Journal of Clinical Investigation·Aleks GuvenelChristopher Chiu
Dec 24, 2019·Critical Reviews in Clinical Laboratory Sciences·Connie WuDavid R Walt
Oct 15, 2020·International Journal of Molecular Sciences·Katharina M QuellYves Laumonnier
Aug 5, 2021·The Journal of Experimental Medicine·Andrea C BohrerKatrin D Mayer-Barber

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Methods Mentioned

BETA
PCR
bronchoalveolar lavage
ELISA
FACS
density gradient centrifugation
blood collection
confocal microscopy
flow cytometry
biopsies

Software Mentioned

Leica Confocal
GraphPad Prism
FlowJo Star

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