Hsp65-producing Lactococcus lactis prevents experimental autoimmune encephalomyelitis in mice by inducing CD4+LAP+ regulatory T cells.

Abstract

Heat shock proteins (Hsps) participate in the cellular response to stress and they are hiperexpressed in inflammatory conditions. They are also known to play a major role in immune modulation, controlling, for instance, autoimmune responses. In this study, we showed that oral administration of a recombinant Lactococcus lactis strain that produces and releases LPS-free Hsp65 prevented the development of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. This was confirmed by the reduced inflammatory cell infiltrate and absence of injury signs in the spinal cord. The effect was associated with reduced IL-17 and increased IL-10 production in mesenteric lymph node and spleen cell cultures. Hsp65-producing-L. lactis-fed mice had a remarkable increase in the number of natural and inducible CD4+Foxp3+ regulatory T (Treg) cells and CD4+LAP+ (Latency-associated peptide) Tregs - which express the membrane-bound TGF-β - in spleen, inguinal and mesenteric lymph nodes as well as in spinal cord. Moreover, many Tregs co-expressed Foxp3 and LAP. In vivo depletion of LAP+ cells abrogated the effect of Hsp65-producing L. lactis in EAE prevention and worsened disease in medium-fed mice. Thus, Hsp65-L.lactis seems to boost this critical regulatory circuit involved in controlling EAE development in mice.

• Authors: Rafael M Rezende, Rafael P Oliveira, Samara R Medeiros, Ana C Gomes-Santos, Andrea C Alves, Flávia G Loli, Mauro A F Guimarães, Sylvia S Amaral, André P da Cunha, Howard L Weiner, Vasco Azevedo, Anderson Miyoshi, Ana M C Faria
• Journal: Journal of autoimmunity (J Autoimmun) Vol. 40 Pg. 45-57 (Feb 2013) ISSN: 1095-9157 [Electronic] England
• PMID: 22939403 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Bacterial Proteins
• CD4 Antigens
• Chaperonin 60
• Forkhead Transcription Factors
• Foxp3 protein, mouse
• Transforming Growth Factor beta
• heat-shock protein 65, Mycobacterium

Topics

• Animals
• Autoimmunity
• Bacterial Proteins (biosynthesis, genetics, metabolism)
• CD4 Antigens (metabolism)
• Chaperonin 60 (biosynthesis, genetics, metabolism)
• Encephalomyelitis, Autoimmune, Experimental (immunology, microbiology, prevention & control)
• Female
• Forkhead Transcription Factors (metabolism)
• Lactococcus lactis (genetics, metabolism)
• Lymph Nodes (immunology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mycobacterium leprae (genetics)
• Spinal Cord (immunology, metabolism)
• Spleen (immunology, metabolism)
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Transforming Growth Factor beta (biosynthesis)