Bacterial Pathogens Hijack the Innate Immune Response by Activation of the Reverse Transsulfuration Pathway

Author:

Gobert Alain P.12,Latour Yvonne L.13,Asim Mohammad1,Finley Jordan L.1,Verriere Thomas G.1,Barry Daniel P.1,Milne Ginger L.4,Luis Paula B.5,Schneider Claus5,Rivera Emilio S.6,Lindsey-Rose Kristie6,Schey Kevin L.6,Delgado Alberto G.1,Sierra Johanna C.1,Piazuelo M. Blanca1,Wilson Keith T.1237

Affiliation:

1. Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA

2. Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee, USA

3. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

4. Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA

5. Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

6. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

7. Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA

Abstract

Macrophages are professional immune cells that ingest and kill microbes. In this study, we show that different pathogenic bacteria induce the expression of cystathionine γ-lyase (CTH) in macrophages. This enzyme is involved in a metabolic pathway called the reverse transsulfuration pathway, which leads to the production of numerous metabolites, including cystathionine. Phagocytized bacteria use cystathionine to better survive in macrophages. In addition, the induction of CTH results in dysregulation of the metabolism of polyamines, which in turn dampens the proinflammatory response of macrophages. In conclusion, pathogenic bacteria can evade the host immune response by inducing CTH in macrophages.

Funder

vetarans health administration

HHS | NIH | National Cancer Institute

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

American Heart Association

HHS | NIH | National Center for Complementary and Integrative Health

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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