TLR-2 independent recognition of Mycobacterium tuberculosis by CD11c+ pulmonary cells from old mice

The elderly are particularly susceptible to infectious diseases such as influenza, bacterial pneumonia. and tuberculosis Current vaccines are only partially protective in old age, which makes the elderly a critical target group for the development of new vaccine strategies The recognition of pathogens via toll like receptors (TLR) and the subsequent generation of pro-inflammatory cytokines has generated interest in incorporating TLR agonists into new vaccines to enhance immunogenicity However. TLR function is reportedly decreased in old age, leading to questions regarding the benefit of including TLR agonists into vaccines for the elderly. It is critical that we understand the function and role of TLRs in aged hosts prior to approving new TLR based adjuvants for vaccines that will be delivered to the elderly. In this study we determine the ability of TLRs on pulmonary macrophages from old mice to recognize and respond to infection with the virulent pathogen Mycobacterium tuberculosis (M. tb). Although pulmonary (CD11c(+)) cells from old mice were fully capable of producing cytokines in response to M tb infection, we demonstrate that in contrast to young mice, M tb induced cytokine production occurred independently of TLR-2 Our data indicate that the inclusion of TLR-2 agonists into new vaccines may not be fully effective in the elderly population. Investigation into such age-related differences in TLR function is of critical importance for the design of effective vaccines that will protect the elderly against infectious diseases (C) 2010 Elsevier Ireland Ltd. All rights reserved.