The microbiome and immune memory formation

Abstract

The microbiota plays an important role in regulating both the innate and adaptive immune systems. Many studies have focused on the ability of microbes to shape the immune system by stimulating B‐cell and antibody responses and the differentiation of T helper cell function. However, an important feature of the immune system is its ability to generate memory responses, which provide increased survival for the host. This review will highlight the role of the microbiota in the induction of immune memory with a focus on both adaptive and innate memory as well as vaccine efficacy.

Innate immune memory of tissue-resident macrophages and trained innate immunity: Re-vamping vaccine concept and strategies

“…While our understanding of the innate immune memory is still evolving, in the present time, innate immune memory is defined as a persisting re‐set homeostatic state of innate immune cells long after the initial Ag or microbial exposure/clearance, thus leading to an altered responsiveness to the same or unrelated Ag or microbe. Therefore, it is currently believed that persisting changes or ongoing anamnestic responses of innate immune cells caused by constant presence of microbes may be a disqualifier for innate immune memory, 22,50 particularly in the absence of the evidence of metabolic/epigenetic reprograming and a persisting functional alteration of innate immune cells independent of the microbe. In this regard, the innate immune tolerance or suppression following pulmonary M.tb exposure occurs as a result of continuing presence of the pathogen and thus may not be considered as a form of innate immune memory, a situation analogous to latent HSV infection 23,51 but dissimilar to innate immune tolerance imparted by acute and transient influenza viral infection discussed above.…”

Immunological memory

“…McCoy et al . review this emerging field, describing what is known about how the microbiome shapes the functionality of innate immune cells, the cytokine milieu and the activation of conventional B and T cells . They outline the substantial impact of the microbiome on the maturation of our immune systems and its potential influence on the outcome of vaccination.…”

“…Clearly, conventional B and T memory cells, virtual memory T cells, and innate cells exhibiting trained memory are functionally poised to respond more rapidly than truly naïve populations to reactivation. The transcriptional profiles of these memory cells are also distinct and this is thought to be mediated by epigenetic changes that make genes for effector mechanisms more accessible and more rapidly expressed with reactivation . Memory cell populations may also be metabolically poised, to meet sudden increases in energy demands upon reactivation .…”

“…McCoy et al and Steigler et al address the role of trained immunity in the interaction of our immune system with our microbiota and in mediating protection against tuberculosis, respectively. 2,4 As another example, virtual memory T cells possess memory-like qualities that are uncoupled from prior antigen exposure. These cells are antigen na€ ıve but semi-differentiated due to cytokine signaling, which permits memory-like function.…”

“…The transcriptional profiles of these memory cells are also distinct and this is thought to be mediated by epigenetic changes that make genes for effector mechanisms more accessible and more rapidly expressed with reactivation. 1,2,4,6,7 Memory cell populations may also be metabolically poised, to meet sudden increases in energy demands upon reactivation. 1,3 There is likely to be substantial cross-regulation of epigenetic marks and metabolic remodeling during activation as each process relies on common substrates.…”