Department of Microbiology and Physiological Systems
Amino Acids, Peptides, and Proteins | Bacteria | Bacterial Infections and Mycoses | Hemic and Immune Systems | Immunity | Immunology of Infectious Disease | Microbiology
Cell-intrinsic immune mechanisms control intracellular pathogens that infect eukaryotes. The intracellular pathogen Mycobacterium tuberculosis (Mtb) evolved to withstand cell-autonomous immunity to cause persistent infections and disease. A potent inducer of cell-autonomous immunity is the lymphocyte-derived cytokine IFNγ. While the production of IFNγ by T cells is essential to protect against Mtb, it is not capable of fully eradicating Mtb infection. This suggests that Mtb evades a subset of IFNγ-mediated antimicrobial responses, yet what mechanisms Mtb resists remains unclear. The IFNγ-inducible Guanylate binding proteins (GBPs) are key host defense proteins able to control infections with intracellular pathogens. GBPs were previously shown to directly restrict Mycobacterium bovis BCG yet their role during Mtb infection has remained unknown. Here, we examine the importance of a cluster of five GBPs on mouse chromosome 3 in controlling Mycobacterial infection. While M. bovis BCG is directly restricted by GBPs, we find that the GBPs on chromosome 3 do not contribute to the control of Mtb replication or the associated host response to infection. The differential effects of GBPs during Mtb versus M. bovis BCG infection is at least partially explained by the absence of the ESX1 secretion system from M. bovis BCG, since Mtb mutants lacking the ESX1 secretion system become similarly susceptible to GBP-mediated immune defense. Therefore, this specific genetic interaction between the murine host and Mycobacteria reveals a novel function for the ESX1 virulence system in the evasion of GBP-mediated immunity.
Microbiology, Mycobacterium tuberculosis, ESX1 secretion system, cytokines
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-ND 4.0 International license.
DOI of Published Version
bioRxiv 2020.07.27.223362; doi: https://doi.org/10.1101/2020.07.27.223362. Link to preprint on bioRxiv service.
Olive AJ, Smith CM, Baer CE, Coers J, Sassetti CM. (2020). Mycobacterium tuberculosis evasion of Guanylate Binding Protein-mediated host defense in mice requires the ESX1 secretion system. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2020.07.27.223362. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1740
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