Suppression of Inflammatory Arthritis by Human Gut-Derived Prevotella histicola in Humanized Mice

Eric V. Marietta, Joseph A Murray, David H. Luckey, Patricio R. Jeraldo, Abhinav Lamba, Robin Patel, Harvinder S. Luthra, Ashutosh Mangalam, Veena D Taneja

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Objective: The gut microbiome regulates host immune homeostasis. Rheumatoid arthritis (RA) is associated with intestinal dysbiosis. This study was undertaken to test the ability of a human gut-derived commensal to modulate immune response and treat arthritis in a humanized mouse model. Methods: We isolated a commensal bacterium, Prevotella histicola, that is native to the human gut and has systemic immune effects when administered enterally. Arthritis-susceptible HLA–DQ8 mice were immunized with type II collagen and treated with P histicola. Disease incidence, onset, and severity were monitored. Changes in gut epithelial proteins and immune response as well as systemic cellular and humoral immune responses were studied in treated mice. Results: When treated with P histicola in prophylactic or therapeutic protocols, DQ8 mice exhibited significantly decreased incidence and severity of arthritis compared to controls. The microbial mucosal modulation of arthritis was dependent on regulation by CD103+ dendritic cells and myeloid suppressors (CD11b+Gr-1+ cells) and by generation of Treg cells (CD4+CD25+FoxP3+) in the gut, resulting in suppression of antigen-specific Th17 responses and increased transcription of interleukin-10. Treatment with P histicola led to reduced intestinal permeability by increasing expression of enzymes that produce antimicrobial peptides as well as tight junction proteins (zonula occludens 1 and occludin). However, the innate immune response via Toll-like receptor 4 (TLR-4) and TLR-9 was not affected in treated mice. Conclusion: Our results demonstrate that enteral exposure to P histicola suppresses arthritis via mucosal regulation. P histicola is a unique commensal that can be explored as a novel therapy for RA and may have few or no side effects.

Original languageEnglish (US)
Pages (from-to)2878-2888
Number of pages11
JournalArthritis and Rheumatology
Volume68
Issue number12
DOIs
StatePublished - Dec 1 2016

Fingerprint

Prevotella
Arthritis
Rheumatoid Arthritis
Dysbiosis
Occludin
Tight Junction Proteins
Toll-Like Receptor 4
Collagen Type II
Tight Junctions
Incidence
Regulatory T-Lymphocytes
Humoral Immunity
Innate Immunity
Cellular Immunity
Interleukin-10
Dendritic Cells
Small Intestine
Permeability
Homeostasis
Bacteria

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Suppression of Inflammatory Arthritis by Human Gut-Derived Prevotella histicola in Humanized Mice. / Marietta, Eric V.; Murray, Joseph A; Luckey, David H.; Jeraldo, Patricio R.; Lamba, Abhinav; Patel, Robin; Luthra, Harvinder S.; Mangalam, Ashutosh; Taneja, Veena D.

In: Arthritis and Rheumatology, Vol. 68, No. 12, 01.12.2016, p. 2878-2888.

Research output: Contribution to journalArticle

Marietta, Eric V. ; Murray, Joseph A ; Luckey, David H. ; Jeraldo, Patricio R. ; Lamba, Abhinav ; Patel, Robin ; Luthra, Harvinder S. ; Mangalam, Ashutosh ; Taneja, Veena D. / Suppression of Inflammatory Arthritis by Human Gut-Derived Prevotella histicola in Humanized Mice. In: Arthritis and Rheumatology. 2016 ; Vol. 68, No. 12. pp. 2878-2888.
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AU - Lamba, Abhinav

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