Piu Saha1, Blair Mell1, Rachel M Golonka1, Venugopal R Bovilla1, Ahmed A Abokor1, Xue Mei1, Beng San Yeoh1, Peter A Doris2, Andrew T Gewirtz3, Bina Joe1, Matam Vijay-Kumar1. 1. UT Microbiome Consortium, Center for Hypertension and Precision Medicine, Department of Physiology & Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH (P.S., B.M., R.M.G., V.R.B., A.A.A., X.M., B.S.Y., B.J., M.V.-K.). 2. Brown Foundation Institute of Molecular Medicine, University of Texas McGovern Medical School, Houston' TX (P.A.D.). 3. Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta' GA (A.T.G.).
Abstract
BACKGROUND: The spontaneously hypertensive rat (SHR) is extensively used to study hypertension. Gut microbiota dysbiosis is a notable feature in SHR for reasons unknown. Immunoglobulin A (IgA) is a major host factor required for gut microbiota homeostasis. We hypothesized that inadequate IgA contributes to gut microbiota dysbiosis in SHR. METHODS: IgA was measured in feces, cecum, serum, liver, gut-associated lymphoid tissue, and milk from SHR and Wistar Kyoto rats. IgA regulatory factors like IgM, IgG, and pIgR (polymeric immunoglobulin receptor) were analyzed. IgA and IgG antibodies and blood pressure (BP) were measured before and after administrating a bacterial antigen (ie, flagellin). RESULTS: Compared with Wistar Kyoto rats, SHR displayed remarkably near-deficient IgA levels accompanied by compensatory increases in serum IgM and IgG and gut-liver pIgR expression. Inadequate milk IgA in SHR emphasized this immune defect stemmed from the neonatal stage. Reduced IgA+ B cells in circulation and Peyer patches indicated a possible reason for the lower IgA in SHR. Noteworthy, a genetic insufficiency was unlikely because administering flagellin to SHR induced anti-flagellin IgA antibodies. This immune response surprisingly accelerated hypertension development in SHR, suggesting IgA quiescence may help maintain lower BP. CONCLUSIONS: This study is the first to reveal IgA deficiency in SHR as one host factor associated with gut microbiota dysbiosis and invigorates future research to determine the pathophysiological role of IgA in hypertension.
BACKGROUND: The spontaneously hypertensive rat (SHR) is extensively used to study hypertension. Gut microbiota dysbiosis is a notable feature in SHR for reasons unknown. Immunoglobulin A (IgA) is a major host factor required for gut microbiota homeostasis. We hypothesized that inadequate IgA contributes to gut microbiota dysbiosis in SHR. METHODS: IgA was measured in feces, cecum, serum, liver, gut-associated lymphoid tissue, and milk from SHR and Wistar Kyoto rats. IgA regulatory factors like IgM, IgG, and pIgR (polymeric immunoglobulin receptor) were analyzed. IgA and IgG antibodies and blood pressure (BP) were measured before and after administrating a bacterial antigen (ie, flagellin). RESULTS: Compared with Wistar Kyoto rats, SHR displayed remarkably near-deficient IgA levels accompanied by compensatory increases in serum IgM and IgG and gut-liver pIgR expression. Inadequate milk IgA in SHR emphasized this immune defect stemmed from the neonatal stage. Reduced IgA+ B cells in circulation and Peyer patches indicated a possible reason for the lower IgA in SHR. Noteworthy, a genetic insufficiency was unlikely because administering flagellin to SHR induced anti-flagellin IgA antibodies. This immune response surprisingly accelerated hypertension development in SHR, suggesting IgA quiescence may help maintain lower BP. CONCLUSIONS: This study is the first to reveal IgA deficiency in SHR as one host factor associated with gut microbiota dysbiosis and invigorates future research to determine the pathophysiological role of IgA in hypertension.
Entities:
Keywords:
B cells; blood pressure; flagellin; gut microbiota; milk; polymeric immunoglobulin receptors
Authors: Bina Joe; Cameron G McCarthy; Jonnelle M Edwards; Xi Cheng; Saroj Chakraborty; Tao Yang; Rachel M Golonka; Blair Mell; Ji-Youn Yeo; Nicole R Bearss; Janara Furtado; Piu Saha; Beng San Yeoh; Matam Vijay-Kumar; Camilla F Wenceslau Journal: Hypertension Date: 2020-10-19 Impact factor: 10.190
Authors: Siegfried Hapfelmeier; Melissa A E Lawson; Emma Slack; Jorum K Kirundi; Maaike Stoel; Mathias Heikenwalder; Julia Cahenzli; Yuliya Velykoredko; Maria L Balmer; Kathrin Endt; Markus B Geuking; Roy Curtiss; Kathy D McCoy; Andrew J Macpherson Journal: Science Date: 2010-06-25 Impact factor: 47.728