microbiota by the immune system, quite apart from leading to a different pattern of
activation of innate immune mechanisms in the airways.
This huge topic will not be reviewed further here, except to note that in addition to
the microbial molecules mentioned above, various PRR detect peptidoglycan monomers, teichoic acids, porins, mycolic acid, mannose-rich glycans, flagellin, and many
others. Thus, the PRR expressed in the airways play a crucial role in setting up
appropriate background immune activation, matched to the load and identity of the
microbes detected (Netea et al. 2016). But perhaps even more important is the role of
airway PRR in setting up immunoregulation, discussed in the next section.
18.4.5 Signals to Set Up Immunoregulation
Studies of protection from allergic disorders by exposure in childhood to the farming
environment have begun to highlight the importance of early exposure to microbederived molecules containing muramic acid, a component of many bacterial cell
walls, or LPS derived from Gram-negative bacteria (Fig. 18.3). For example, levels
of muramic acid in the home, or levels of LPS in the child’s mattress during the first
year of life correlated with a lower prevalence of school-age asthma, and mattress
Fig. 18.3 Signals from the natural environment that drive immunoregulation. Signals such as that
provided by endotoxin (LPS) initially drive inflammation, but if repeated in small doses they drive
“endotoxin tolerance”, which ultimately results in raised activity of anti-inflammatory pathways and
mediators, and increased regulatory lymphocytes (Tr1, Treg), and mediators (IL-10). Most, perhaps
all, pathogen-associated molecular patterns (PAMPS) do this, and so balance the activation of the
innate immune system known as “trained immunity”. Similarly, molecules of plant origin that often
accompany microorganisms in biogenic aerosols and pollen grains can also provide antiinflammatory signals
18 Darwinian Medicine: We Evolved to Require Continuing Contact with the. . .
341
activation of innate immune mechanisms in the airways.
This huge topic will not be reviewed further here, except to note that in addition to
the microbial molecules mentioned above, various PRR detect peptidoglycan monomers, teichoic acids, porins, mycolic acid, mannose-rich glycans, flagellin, and many
others. Thus, the PRR expressed in the airways play a crucial role in setting up
appropriate background immune activation, matched to the load and identity of the
microbes detected (Netea et al. 2016). But perhaps even more important is the role of
airway PRR in setting up immunoregulation, discussed in the next section.
18.4.5 Signals to Set Up Immunoregulation
Studies of protection from allergic disorders by exposure in childhood to the farming
environment have begun to highlight the importance of early exposure to microbederived molecules containing muramic acid, a component of many bacterial cell
walls, or LPS derived from Gram-negative bacteria (Fig. 18.3). For example, levels
of muramic acid in the home, or levels of LPS in the child’s mattress during the first
year of life correlated with a lower prevalence of school-age asthma, and mattress
Fig. 18.3 Signals from the natural environment that drive immunoregulation. Signals such as that
provided by endotoxin (LPS) initially drive inflammation, but if repeated in small doses they drive
“endotoxin tolerance”, which ultimately results in raised activity of anti-inflammatory pathways and
mediators, and increased regulatory lymphocytes (Tr1, Treg), and mediators (IL-10). Most, perhaps
all, pathogen-associated molecular patterns (PAMPS) do this, and so balance the activation of the
innate immune system known as “trained immunity”. Similarly, molecules of plant origin that often
accompany microorganisms in biogenic aerosols and pollen grains can also provide antiinflammatory signals
18 Darwinian Medicine: We Evolved to Require Continuing Contact with the. . .
341