Modeling of variables in cellular infection reveals CXCL10 levels are regulated by human genetic variation and the Chlamydia-encoded CPAF protease.

Journal Article (Journal Article)

Susceptibility to infectious diseases is determined by a complex interaction between host and pathogen. For infections with the obligate intracellular bacterium Chlamydia trachomatis, variation in immune activation and disease presentation are regulated by both host genetic diversity and pathogen immune evasion. Previously, we discovered a single nucleotide polymorphism (rs2869462) associated with absolute abundance of CXCL10, a pro-inflammatory T-cell chemokine. Here, we report that levels of CXCL10 change during C. trachomatis infection of cultured cells in a manner dependent on both host and pathogen. Linear modeling of cellular traits associated with CXCL10 levels identified a strong, negative correlation with bacterial burden, suggesting that C. trachomatis actively suppresses CXCL10. We identified the pathogen-encoded factor responsible for this suppression as the chlamydial protease- or proteasome-like activity factor, CPAF. Further, we applied our modeling approach to other host cytokines in response to C. trachomatis and found evidence that RANTES, another T-cell chemoattractant, is actively suppressed by Chlamydia. However, this observed suppression of RANTES is not mediated by CPAF. Overall, our results demonstrate that CPAF suppresses CXCL10 to evade the host cytokine response and that modeling of cellular infection parameters can reveal previously unrecognized facets of host-pathogen interactions.

Full Text

Duke Authors

Cited Authors

  • Schott, BH; Antonia, AL; Wang, L; Pittman, KJ; Sixt, BS; Barnes, AB; Valdivia, RH; Ko, DC

Published Date

  • October 26, 2020

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 18269 -

PubMed ID

  • 33106516

Pubmed Central ID

  • PMC7588472

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/s41598-020-75129-y

Language

  • eng

Conference Location

  • England