Open AccessFlagellin‐dependent TLR 5/caveolin‐1 as a promising immune activator in immunosenescence
Author(s) -
Lim Jae Sung,
Nguyen Kim Cuc Thi,
Nguyen Chung Truong,
Jang IkSoon,
Han Jung Min,
Fabian Claire,
Lee Shee Eun,
Rhee Joon Haeng,
Cho Kyung A
Publication year - 2015
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12383
Subject(s) - flagellin , immune system , biology , streptococcus pneumoniae , immunology , innate immune system , adjuvant , immunosenescence , spleen , downregulation and upregulation , receptor , microbiology and biotechnology , biochemistry , antibiotics , gene
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 ( TLR 5), unlike the other TLR s, were well maintained in old macrophages, similar to young macrophages. The expression and activation of TLR 5/MyD88, but not TLR 4, 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 TLR 5 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/ TLR 5 signaling plays a key role in age‐associated innate immune responses and that FlaB‐PspA stimulation of TLR 5 may be a new strategy for a mucosal vaccine adjuvant against pneumococcal infection in the elderly.