Gut microbiota–dependent modulation of innate immunity and lymph node remodeling affects cardiac allograft outcomes
Jonathan S. Bromberg, Lauren Hittle, Yanbao Xiong, Vikas Saxena, Eoghan M. Smyth, Lushen Li, Tianshu Zhang, Chelsea Wagner, W. Florian Fricke, Thomas Simon, Colin C. Brinkman, and Emmanuel F. Mongodin
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Published August 6, 2020 - More info
JCI Insight. 2020;5(15):e142528. https://doi.org/10.1172/jci.insight.142528.
© 2020 The American Society for Clinical Investigation
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Abstract
We hypothesized that the gut microbiota influences survival of murine cardiac allografts through modulation of immunity. Antibiotic pretreated mice received vascularized cardiac allografts and fecal microbiota transfer (FMT), along with tacrolimus immunosuppression. FMT source samples were from normal, pregnant (immune suppressed), or spontaneously colitic (inflammation) mice. Bifidobacterium pseudolongum (B. pseudolongum) in pregnant FMT recipients was associated with prolonged allograft survival and lower inflammation and fibrosis, while normal or colitic FMT resulted in inferior survival and worse histology. Transfer of B. pseudolongum alone resulted in reduced inflammation and fibrosis. Stimulation of DC and macrophage lines with B. pseudolongum induced the antiinflammatory cytokine IL-10 and homeostatic chemokine CCL19 but induced lesser amounts of the proinflammatory cytokines TNFα and IL-6. In contrast, LPS and Desulfovibrio desulfuricans (D. desulfuricans), more abundant in colitic FMT, induced a more inflammatory cytokine response. Analysis of mesenteric and peripheral lymph node structure showed that B. pseudolongum gavage resulted in a higher laminin α4/α5 ratio in the lymph node cortical ridge, indicative of a suppressive environment, while D. desulfuricans resulted in a lower laminin α4/α5 ratio, supportive of inflammation. Discrete gut bacterial species alter immunity and may predict graft outcomes through stimulation of myeloid cells and shifts in lymph node structure and permissiveness.
Authors
Jonathan S. Bromberg, Lauren Hittle, Yanbao Xiong, Vikas Saxena, Eoghan M. Smyth, Lushen Li, Tianshu Zhang, Chelsea Wagner, W. Florian Fricke, Thomas Simon, Colin C. Brinkman, Emmanuel F. Mongodin
Original citation: JCI Insight. 2018;3(19):e121045. https://doi.org/10.1172/jci.insight.121045
Citation for this corrigendum: JCI Insight. 2020;5(15):e142528. https://doi.org/10.1172/jci.insight.142528
B. pseudolongum subsp. pseudolongum Mitsuoka (ATCC25526; https://www.atcc.org/products/all/25526.aspx) was incorrectly described as a human isolate. B. pseudolongum strain ATCC25526 is a swine isolate. The changes this necessitates are below.
In the section Graft survival and histology in Results, the last four sentences should be changed to the following: It is important to note that B. pseudolongum ATCC25526 is a swine isolate and not mouse adapted yet was active in this in vivo assay. It will be interesting in future investigations to use murine-adapted or -derived species.
In the final paragraph of Results, the fourth sentence should read as follows: As noted above, the B. pseudolongum ATCC25526 strain is swine derived and not murine adapted.
The authors regret the errors.
