Streptococcus agalactiae and Escherichia coli Induce Distinct Effector γδ T Cell Responses During Neonatal Sepsis and Neuroinflammation

The neonatal phase of life is a time during which susceptibility to infection is particularly high, with prematurely born neonates being especially vulnerable to life-threatening conditions such as bacterial sepsis. While Streptococcus agalactiae, also known as group B Streptococcus (GBS) and Escherichia coli are frequent causative pathogens of neonatal sepsis, it is still unclear how the neonatal adaptive immune system responds to these pathogens. In the present study, we find that γδ T cells in neonatal mice rapidly respond to single-organism sepsis infections of GBS and E. coli, and that these infections induce distinct activation and effector functions from IFN-γ and IL-17 producing γδ T cells, respectively. We also report differential reliance on γδTCR signaling to elicit effector cytokine responses during neonatal sepsis, with IL-17 production during E. coli sepsis being associated with TCR signaling, whereas IFN-γ production during GBS sepsis is TCR-independent. Furthermore, we report that the divergent effector responses of γδ during GBS and E. coli sepsis impart distinctive neuroinflammatory phenotypes on the neonatal brain. The present study sheds light on how the neonatal adaptive immune response responds differentially to bacterial stimuli and how these responses impact neonatal sepsis-associated neuroinflammation.