Development of T cell immunity to Listeria monocytogenes and Mycobacterium tuberculosis-dendritic cells as an 'Achilles' Heel' and immune deficiency in dopamine beta-hydroxylase knock-out mice

Protective immunity against microbial infection is an elegant and complicated interplay of host defenses and microbial evasion. On top of that, host physiology can influence the quality of protective immunity. We have addressed how seemingly unrelated factors, dendritic cells (DCs) and catecholamines, affect the development of T cell immunity during infection with the intracellular bacteria Listeria monocytogenes and Mycobacterium tuberculosis.; Augmentation of immunity to infection by manipulation of host endogenous factors is an ambitious goal of modern immunology. We have examined an aspect of this, in the context of Listeria infection, by increasing numbers of DCs in vivo and characterizing how this leads to an amplification of adaptive T cell responses. Our work is further evidence of the potent T cell activating capacity DCs have in promoting and augmenting immunity against tumor challenge and microbial infection. However, we have illuminated novel aspects of DC biology that allows DCs to be reservoirs for intracellular bacteria despite the presence of enhanced T cell immunity. Our results demonstrate DCs are not designed to be efficient microbial killers or to be easily lysed by cytotoxic T lymphocytes. These qualities may be intrinsic to a DC's role as an antigen presenting cell, but they can also be an “Achilles' Heel” for the host by allowing intracellular bacteria, such as Listeria and M. tuberculosis, to persist.; In addition, the role of neuroendocrine factors in the development of T cell immunity against infection was examined. The role of catecholamines in host defense is unclear. We have addressed an aspect of this in dopamine β-hydroxylase-deficient mice (dbh −/− mice), which lack noradrenaline and adrenaline but have elevated levels of dopamine. Dbh −/− mice proved to more susceptible to infection due to the inhibition of T cell mediated protective immunity against Listeria and M. tuberculosis infection.; The work presented here illustrates how host defenses to infection can be undermined in the presence of high numbers of a normally beneficial cell type and in the context of a disregulated neuroendocrine system.