Caveolae-mediated entry of Salmonella typhimurium into senescent nonphagocytotic host cells.
Elderly individuals have an increased susceptibility to microbial infections because of age-related anatomical, physiological, and environmental factors. However, the mechanism of aging-dependent susceptibility to infection is not fully understood. Here, we found that caveolae-dependent endocytosis is elevated in senescent cells. Thus, we focused on the implications of caveolae-dependent endocytosis using Salmonella typhimurium, which causes a variety of diseases in humans and animals by invading the eukaryotic host cell. Salmonella invasion increased in nonphagocytotic senescent host cells in which caveolin-1 was also increased. When caveolae structures were disrupted by methyl-beta-cyclodextrin or siRNA of caveolin-1 in the senescent cells, Salmonellae invasion was reduced markedly compared to that in nonsenescent cells. In contrast, the over-expression of caveolin-1 led to increased Salmonellae invasion in nonsenescent cells. Moreover, in aged mice, caveolin-1 was found to be highly expressed in Peyer's patch and spleen, which are targets for infection by Salmonellae. These results suggest that high levels of caveolae and caveolin-1 in senescent host cells might be related to the increased susceptibility of elderly individuals to microbial infections.
Lim
Jae Sung
JS
Department of Biochemistry, Chonnam National University Medical School, Gwangju, Korea.
Choy
Hyon E
HE
Park
Sang Chul
SC
Han
Jung Min
JM
Jang
Ik-Soon
IS
Cho
Kyung A
KA
D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D021941:Caveolae / Q000502:physiology*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D012486:Salmonella typhimurium / Q000502:physiology*
D051242:Caveolin 1