Group B Streptococcus (GBS ) is a common commensal bacterium for healthy adults. Approximately 20% of
women are infected with GBS in the genitourinary tract without symptoms. However, GBS can cause serious
disease in newborn infants. A majority of newborn infants from colonized women get infected with GBS, and
about 1% of these infants develop sepsis. Indeed, GBS is a leading cause of invasive infections in infants. GBS
infection can be lethal for preterm babies. Moreover, approximately 50% of GBS meningitis survivors suffer
lifelong neurological impairment. Thus, it is critically important to understand how GBS colonizes infants and
what causes invasive infection by GBS to improve the health care of newborns.
Infants have a suppressed immune system which makes them highly vulnerable to infections and limits
their immune responses to protective and life-saving vaccines. Both adaptive and innate immune responses in
the infant are less effective than those in adult. However, how infant immunity differs from adult immunity in
understudies and requires more investigations.
GBS has unique capabilities to modulate the human immune system. One such mechanism is the
immune inhibition by GBS's cell wall-anchored ß–protein. This protein binds to a complement regulatory
factor H and the constant region of IgA. Moreover, the GBS ß protein binds a C-type Sialic acid-binding
immunoglobulin-like lectin 5 (Siglec) 5. Siglec 5 is a cell surface protein expressed by many types of myeloid
cells and has a cytoplasmic domain with two immunosuppressive motifs: immunoreceptor tyrosine-based
inhibitory motif (ITIM) and immunoreceptor tyrosine-based switch motif (ITSM). Siglec 5 was shown to
suppress activation of neutrophils and macrophages but was reported previously not expressed by human T
cells. Importantly, our sequence alignment analysis showed that the cytoplasmic region of Siglec 5 is closely
related to a prototypic immune checkpoint molecule PD-1.
To test if GBS modulates perinatal immune responses by ß protein-Siglec 5 interactions, we examined
the expression of Siglec 5 by cord blood cells in our preliminary study. Unlike previous reports, our data show
that a majority of activated cord blood and adult blood T cells express Siglec 5. Siglec 5 expressions in a T cell
line inhibited antigen receptor-induced activation of transcription factors. Moreover, recombinant GBS ß
protein suppressed primary T cell responses, especially Th1 type cytokine productions. Thus, Siglec 5 is a
potential immune checkpoint molecule that was not previously recognized.
Based on these data, we hypothesize that GBS inhibits activation of perinatal T cells upon infection by ß
protein-Siglec 5 interactions and reduces adaptive immune responses. In this study, we aim to pursue the
following two questions. (1) How does the GBS ß protein change T cell activation? (2) Is Siglec 5 required for
the T cell suppression by GBS-ß protein?