Aging-related changes in lymphatic collectors predispose to pathogen dissemination in tissues
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abstract
AbstractHerein we analyze how the aging process affects the structure and functionality of the lymphatic collectors (LCs) with reference to their ability to maintain pathogen clearance. Ultrastructural, biochemical and proteomic analysis indicated a loss of extracellular matrix proteins, an increase in protein oxidative modifications as well as activation of nuclear factor-B signaling as sign of low grade inflammation in aged LCs. This resulted in a decrease in contractile and pumping activity of LCs, as measured in vivo. Functionally, this impairment also translated into a reduced ability for in vivo bacterial transport as determined by time-lapse microscopy. Ultrastructural and proteomic analysis also indicated a decrease in the thickness of the endothelial cell glycocalyx and loss of gap-junction proteins in aged LCs. Redox proteomic analysis mapped an aging-related increase in the glycation and carboxylation of endothelial cell glycocalyx structural proteins. Functionally, these modifications translated into higher ability of the pathogen to escape from aged LCs into the surrounding tissue. Altogether, our analysis mapped the complexity of the aging-related anatomical, biochemical and functional changes in LCs. The decreased ability to transport bacteria to the draining nodes, associated with increased bacterial escape in the surrounding tissue can contribute to the decreased ability of the immune system to clear pathogens in the elderly, as observed in immunosenescence.
