Aging mice exhibit a functional defect in mucosal dendritic cell response against an intracellular pathogen.
Down-regulation of the immune response in aging individuals puts this population at a potential risk against infectious agents. In-depth studies conducted in humans and mouse models have demonstrated that with increasing age, the T cell immune response against pathogens is compromised and response to vaccinations is subdued. In the present study, using a mouse model, we demonstrate that older animals exhibit greater susceptibility to Encephalitozoon cuniculi infection, and their ability to evoke an Ag-specific T cell response at the gut mucosal site is reduced. The dampening of T cell immunity was due to the defective priming by the dendritic cells (DC) isolated from the mucosal tissues of aging animals. When primed with DC from younger mice, T cells from older animals were able to exhibit an optimal Ag-specific response. The functional defect in DC from older mice can be attributed to a large extent to reduced IL-15 message in these cells, which can be reversed by addition of exogenous IL-15 to the cultures. IL-15 treatment led to optimal expression of costimulatory molecules (CD80 and CD86) on the surface of older DC and restored their ability to prime a T cell response against the pathogen. To our knowledge, this is the first report which demonstrates the inability of the DC population from aging animals to prime a robust T cell response against an infectious agent. Moreover, the observation that IL-15 treatment can reverse this defect has far-reaching implications in developing strategies to increase vaccination protocols for aging populations.
Moretto
Magali M
MM
Department of Microbiology, Immunology and Tropical Medecine, George Washington University, Washington, DC 20037, USA.
Lawlor
Elizabeth M
EM
Khan
Imtiaz A
IA
D000375:Aging / Q000276:immunology* / Q000473:pathology; D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D009670:Encephalitozoon cuniculi / Q000276:immunology*; D016890:Encephalitozoonosis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D019409:Interleukin-15 / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D000946:Antigens, Fungal; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D019409:Interleukin-15