Flagellin‐dependent TLR5/caveolin‐1 as a promising immune activator in immunosenescence

Aging Cell

Jae Sung Lim⁵  Kim Cuc Thi Nguyen⁵  Chung Truong Nguyen⁴  Ik-Soon Jang¹  Jung Min Han²  Claire Fabian³  Shee Eun Lee⁴  Joon Haeng Rhee⁴ 

[1] Division of Life Science, Korea Basic Science Institute, Daejeon, South Korea;Department of Integrated OMICS for Biomedical Science, Yonsei University, Seoul, South Korea;Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology (IZI), University of Leipzig, Leipzig, Germany;Clinical Vaccine R&D Center, Chonnam National University Hwasun Hospital, Jeonnam, South Korea;Department of Biochemistry, Chonnam National University Medical School, Gwangju, South Korea

关键词: immunosenescence;    vaccine adjuvant;    TLR5;    flagellin;    caveolin‐1;   

DOI  :  10.1111/acel.12383

来源: Wiley

【 摘 要 】

Summary

The age-associated decline of immune responses causes high susceptibility to infections and reduced vaccine efficacy in the elderly. However, the mechanisms underlying age-related deficits are unclear. Here, we found that the expression and signaling of flagellin (FlaB)-dependent Toll-like receptor 5 (TLR5), unlike the other TLRs, were well maintained in old macrophages, similar to young macrophages. The expression and activation of TLR5/MyD88, but not TLR4, were sensitively regulated by the upregulation of caveolin-1 in old macrophages through direct interaction. This interaction was also confirmed using macrophages from caveolin-1 or MyD88 knockout mice. Because TLR5 and caveolin-1 were well expressed in major old tissues including lung, skin, intestine, and spleen, we analyzed in vivo immune responses via a vaccine platform with FlaB as a mucosal adjuvant for the pneumococcal surface protein A (PspA) against Streptococcus pneumoniae infection in young and aged mice. The FlaB-PspA fusion protein induced a significantly higher level of PspA-specific IgG and IgA responses and demonstrated a high protective efficacy against a lethal challenge with live S. pneumoniae in aged mice. These results suggest that caveolin-1/TLR5 signaling plays a key role in age-associated innate immune responses and that FlaB-PspA stimulation of TLR5 may be a new strategy for a mucosal vaccine adjuvant against pneumococcal infection in the elderly.

【 授权许可】

CC BY   
© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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