What is already known
The development of a child’s immune system is influenced by factors such as the transfer of antibodies from the mother. However, it’s unclear how other components of a mother’s immune system affect the offspring’s immune status.
What this research adds
Researchers have found that, compared with controls, mice born from mothers that lack a type of immune cells known as γδ T cells show increased lung inflammation following the “first breath response,” an immune reaction that results in lung tissue remodeling when the lungs are filled with gas after birth. Upon infection, these mice have a heightened inflammatory response. They also harbor a different gut microbiota from control mice and have reduced levels of beneficial short-chain fatty acids (SCFAs) in their guts. Supplementing mice with SCFAs reduces inflammation after both infection and first breath response.
Conclusions
The findings suggest that a newborn’s lung immunity is influenced by the interplay between maternal γδ T cells, the gut microbiota and microbial-derived SCFAs.
The development of a child’s immune system is influenced by several maternal factors, but how specific components of a mother’s immune system influence a newborn’s immune status remains a mystery. Working in mice, researchers have now found that maternal γδ T cells, a type of immune cells, are involved in the development of lung immunity in the offspring. The cells appear to exert an effect on the pups’ gut bacteria and on short-chain fatty acids (SCFAs), a type of microbial metabolites that have been shown to promote health.
The findings, published in Cell Reports, suggest that a newborn’s lung immunity is influenced by the interplay between maternal γδ T cells, the gut microbiota and microbial-derived SCFAs.
The transfer of antibodies from the mother is known to influence the development of the offspring’s immune system. However, it’s unclear how other components of the maternal immune system affect a newborn’s immune status. For example, the γδ T cells are a type of white blood cells that reside in the female reproductive tract, the skin and the mammary glands. These cells are known to control antibody production and participate in a cross-talk with the microbiota, but their role in the development of the newborn’s immune system is unknown.
To fill this knowledge gap, researchers led by Pedro Papotto at the University of Manchester and Bruno Silva-Santos at the University of Lisbon set out to investigate how maternal γδ T cells influence the maturation of the immune system of newborn mice.
Immune development
In the first breath after birth, the liquid that fills the lungs is replaced by gas. This causes an immune reaction called “first breath response,” which results in lung tissue remodeling. Compared with controls, mice born from mothers lacking γδ T cells showed increased lung inflammation following the first breath response, the researchers found.
The pups’ lungs were enriched in immune cells and molecules associated with a type of immune response that drives tissue inflammation and causes tissue changes such as swelling, itching and pain. Pups born from mothers lacking γδ T cells that were treated with antibiotics had similar lung levels of immune molecules to controls.
Pups born from mothers with γδ T cells had increased abundances of Rikenellaceae, Muribaculaceae and Lachnospiraceae, whereas those born from mothers lacking γδ T cells showed higher levels of Lachnoclostridium. Compared to controls, these pups also showed reduced levels of short-chain fatty acids (SCFAs), a class of microbial metabolites that have been shown to promote health.
Preventing inflammation
When infected with a parasite that affects the lungs, pups born from mothers without γδ T cells showed increased lung damage compared with controls. However, supplementing mice with SCFAs reduced inflammation after infection, the researchers found.
Microbial-derived SCFAs also prevent exacerbated lung inflammation after immune activation induced by the first breath response.
The findings, the researchers say, “suggest that maternal γδ T cells regulate postnatal microbial colonization and microbial-derived metabolite availability in the offspring, ultimately impacting the pulmonary immune system development.” However, they note, more work is needed to identify the mechanism by which these cells change microbiota composition.
