Age-Dependent Differences in Systemic and Cell-Autonomous Immunity toL. monocytogenes

Abstract

Host defense against infection can broadly be categorized into systemic immunity and cell-autonomous immunity. Systemic immunity is crucial for all multicellular organisms, increasing in importance with increasing cellular complexity of the host. The systemic immune response to Listeria monocytogenes has been studied extensively in murine models; however, the clinical applicability of these findings to the human newborn remains incompletely understood. Furthermore, the ability to control infection at the level of an individual cell, known as “cell-autonomous immunity,” appears most relevant following infection with L. monocytogenes; as the main target, the monocyte is centrally important to innate as well as adaptive systemic immunity to listeriosis. We thus suggest that the overall increased risk to suffer and die from L. monocytogenes infection in the newborn period is a direct consequence of age-dependent differences in cell-autonomous immunity of the monocyte to L. monocytogenes. We here review what is known about age-dependent differences in systemic innate and adaptive as well as cell-autonomous immunity to infection with Listeria monocytogenes.

RTX Toxin Plays a Key Role in Kingella kingae Virulence in an Infant Rat Model

“…During this early stages of life, neutrophils and monocytes together make up progressively less of the total WBC population, which correlates with susceptibility to Haemophilus influenzae pneumonia and otitis media (44,45). Interestingly, animal models have demonstrated that depleting neutrophils prior to pathogen inoculation can increase the pathogen burden, which has been shown for a Listeria monocytogenes disease model (46,47). Additionally, a depletion of monocytes can increase the risk of death from listerial infection (48).…”

Listeria monocytogenes

“…91 Lm-activated signaling pathways in the neonate The particularly high risk of severe outcome from Lm infection in the newborn suggests that possible differences exist between the immune signaling pathways activated by Lm in neonates vs. the adult. 103,104 The importance of the MyD88-dependent pathway for host resistance is clearly seen from the extreme vulnerability displayed by MyD88-deficient mice to Lm infection. 105,106 Even though the ability for innate recognition of pathogens via the TLR/MyD88 pathway early in life does not appear to be different compared with adults, 107 there are stark contrasts between the downstream effector responses generated in the human newborn as compared with the young adult 103,104 (discussed in the following section).…”

“…The TLR/MyD88-dependent response of human neonatal monocytes specifically to Lm infection has yet to be explored. 104 While IRF3-dependent production of type I IFN via the STING/IRF3-dependent pathway in human newborns is reduced compared with adults, 103 the production of IFN-β in humans in response to Lm appears not IRF3-dependent but instead, p38 MAPK-dependent. 108 The role of the STING/IRF-3 pathway in human neonatal Lm infection is thus still unclear.…”

“…108 The role of the STING/IRF-3 pathway in human neonatal Lm infection is thus still unclear. 104 Finally, although the developmental patterns of the various inflammasome pathways in humans in response to Lm have not been unravelled, it is known that activation of the inflammasome is one way through which aluminum hydroxide (alum, the most common vaccine adjuvant) exerts its function. 109 Given that innate immune responses induced by alum decrease over the first 2 y of life, 110 age-dependent differences in at least some inflammasome activities are likely to exist.…”

“…109 Given that innate immune responses induced by alum decrease over the first 2 y of life, 110 age-dependent differences in at least some inflammasome activities are likely to exist. 104 This has, however, not been investigated in relation to Lm. 104 Immune response to Lm in the neonate Splenocytes from infected neonates of a murine neonatal listeriosis model have been shown to exhibit much lower expression levels of Th1-supporting cytokines (IL-12p70 and IFN-γ), even when presented with Th1-driving stimuli.…”