Selected commensals educate the intestinal vascular and immune system for immunocompetence

Author:

Romero Rossana,Zarzycka Agnieszka,Preussner Mathieu,Fischer Florence,Hain Torsten,Herrmann Jan-Paul,Roth Katrin,Keber Corinna U.,Suryamohan Kushal,Raifer Hartmann,Luu Maik,Leister Hanna,Bertrams Wilhelm,Klein Matthias,Shams-Eldin Hosam,Jacob Ralf,Mollenkopf Hans-Joachim,Rajalingam Krishnaraj,Visekruna Alexander,Steinhoff UlrichORCID

Abstract

Abstract Background The intestinal microbiota fundamentally guides the development of a normal intestinal physiology, the education, and functioning of the mucosal immune system. The Citrobacter rodentium-carrier model in germ-free (GF) mice is suitable to study the influence of selected microbes on an otherwise blunted immune response in the absence of intestinal commensals. Results Here, we describe that colonization of adult carrier mice with 14 selected commensal microbes (OMM12 + MC2) was sufficient to reestablish the host immune response to enteric pathogens; this conversion was facilitated by maturation and activation of the intestinal blood vessel system and the step- and timewise stimulation of innate and adaptive immunity. While the immature colon of C. rodentium-infected GF mice did not allow sufficient extravasation of neutrophils into the gut lumen, colonization with OMM12 + MC2 commensals initiated the expansion and activation of the visceral vascular system enabling granulocyte transmigration into the gut lumen for effective pathogen elimination. Conclusions Consortium modeling revealed that the addition of two facultative anaerobes to the OMM12 community was essential to further progress the intestinal development. Moreover, this study demonstrates the therapeutic value of a defined consortium to promote intestinal maturation and immunity even in adult organisms.

Funder

Von-Behring-Röntgen-Stiftung

Jürgen Manchot Stiftung

Deutsche Forschungsgemeinschaft

Hessisches Ministerium für Wissenschaft und Kunst

Philipps-Universität Marburg

Publisher

Springer Science and Business Media LLC

Subject

Microbiology (medical),Microbiology

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