Early Immunomodulatory Program Triggered by Protolerogenic Bifidobacterium pseudolongum Drives Cardiac Transplant Outcomes.

Autor:	Gavzy SJ; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD.; Department of Surgery, University of Maryland School of Medicine, Baltimore, MD., Kensiski A; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD., Saxena V; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD., Lakhan R; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD., Hittle L; University of Maryland School of Medicine, Institute for Genome Sciences, Baltimore, MD., Wu L; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD., Iyyathurai J; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD., Dhakal H; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD., Lee ZL; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD., Li L; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD.; Department of Surgery, University of Maryland School of Medicine, Baltimore, MD., Lee YS; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD.; Department of Surgery, University of Maryland School of Medicine, Baltimore, MD., Zhang T; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD.; Department of Surgery, University of Maryland School of Medicine, Baltimore, MD., Lwin HW; University of Maryland School of Medicine, Institute for Genome Sciences, Baltimore, MD., Shirkey MW; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD., Paluskievicz CM; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD.; Department of Surgery, University of Maryland School of Medicine, Baltimore, MD., Piao W; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD., Mongodin EF; University of Maryland School of Medicine, Institute for Genome Sciences, Baltimore, MD., Ma B; University of Maryland School of Medicine, Institute for Genome Sciences, Baltimore, MD.; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD., Bromberg JS; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD.; Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD.
Jazyk:	angličtina
Zdroj:	Transplantation [Transplantation] 2024 Jul 01; Vol. 108 (7), pp. e91-e105. Date of Electronic Publication: 2024 Apr 08.
DOI:	10.1097/TP.0000000000004939
Abstrakt:	Background: Despite ongoing improvements to regimens preventing allograft rejection, most cardiac and other organ grafts eventually succumb to chronic vasculopathy, interstitial fibrosis, or endothelial changes, and eventually graft failure. The events leading to chronic rejection are still poorly understood and the gut microbiota is a known driving force in immune dysfunction. We previously showed that gut microbiota dysbiosis profoundly influences the outcome of vascularized cardiac allografts and subsequently identified biomarker species associated with these differential graft outcomes. Methods: In this study, we further detailed the multifaceted immunomodulatory properties of protolerogenic and proinflammatory bacterial species over time, using our clinically relevant model of allogenic heart transplantation. Results: In addition to tracing longitudinal changes in the recipient gut microbiome over time, we observed that Bifidobacterium pseudolongum induced an early anti-inflammatory phenotype within 7 d, whereas Desulfovibrio desulfuricans resulted in a proinflammatory phenotype, defined by alterations in leukocyte distribution and lymph node (LN) structure. Indeed, in vitro results showed that B pseudolongum and D desulfuricans acted directly on primary innate immune cells. However, by 40 d after treatment, these 2 bacterial strains were associated with mixed effects in their impact on LN architecture and immune cell composition and loss of colonization within gut microbiota, despite protection of allografts from inflammation with B pseudolongum treatment. Conclusions: These dynamic effects suggest a critical role for early microbiota-triggered immunologic events such as innate immune cell engagement, T-cell differentiation, and LN architectural changes in the subsequent modulation of protolerant versus proinflammatory immune responses in organ transplant recipients. Competing Interests: This work was supported by the National Institute of Health (NIH), National Heart, Lung, and Blood Institute award R01HL148672 (J.S.B./B.M.), U01AI170050 (B.M./J.S.B.), and National Institute of Allergy and Infectious Diseases training grant T32AI95190-10 (S.J.G.). An earlier version of this article has been released as a preprint on bioRxiv ( https://doi.org/10.1101/2022.10.13.511915 ). E.F.M. contributed to this work as an employee of the University of Maryland School of Medicine. The views expressed in this article are his own and do not necessarily represent the views of the NIH or the US Government. The other authors declare no conflicts of interest. (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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