Abstract
BACKGROUND: It is generally accepted that aging has detrimental effects on conventional T cell responses to systemic infections. However, most pathogens naturally invade the body through mucosal barriers. Although mucosal sites are highly enriched in unconventional immune sentinels like γδ T cells, little is currently known about the impact of aging on unconventional mucosal T cell responses. We previously established that foodborne infection with a mouse-adapted internalin A mutant Listeria monocytogenes (Lm) generates an adaptive intestinal memory CD44(hi) CD27(neg) Vγ4 T cells capable of co-producing IL-17A and IFNγ. Therefore, we used this model to evaluate the impact of aging on adaptive Vγ4 T cell responses elicited by foodborne infection. RESULTS: Foodborne Lm infection of female Balb/c and C57BL/6 mice led to an increased adaptive CD44(hi) CD27(neg) Vγ4 T cell response associated with aging. Moreover, Lm-elicited CD44(hi) CD27(neg) Vγ4 T cells maintained diverse functional subsets despite some alterations favoring IL-17A production as mice aged. In contrast to the documented susceptibility of aged mice to intravenous Lm infection, mice contained bacteria after foodborne Lm infection suggesting that elevated bacterial burden was not a major factor driving the increased adaptive CD44(hi) CD27(neg) Vγ4 T cell response associated with mouse age. However, CD44(hi) CD27(neg) Vγ4 T cells accumulated in naïve mice as they aged suggesting that an increased precursor frequency contributes to the robust Lm-elicited mucosal response observed. Body mass did not appear to have a strong positive association with CD44(hi) CD27(neg) Vγ4 T cells within age groups. Although an increased adaptive CD44(hi) CD27(neg) Vγ4 T cell response may contribute to foodborne Lm resistance of C57BL/6 mice aged 19 or more months, neither anti-TCRδ or anti-IL-17A treatment impacted Lm colonization after primary infection. These results suggest that γδTCR signaling and IL-17A are dispensable for protection after primary foodborne Lm infection consistent with the role of conventional T cells during the early innate immune response to Lm. CONCLUSIONS: Lm-elicited adaptive Vγ4 T cells appear resistant to immunosenescence and memory Vγ4 T cells could be utilized to provide protective immune functions during enteric infection of aged hosts. As such, oral immunization might offer an efficient therapeutic approach to generate unconventional memory T cells in the elderly.