Role of Toll-like receptor 2 in innate resistance to Group B Streptococcus

Abstract

The Gram-positive bacterium Group B Streptococcus (GBS) is an important cause of serious neonatal and adult infections. Toll-like receptor 2 (TLR2) recognizes components of the cell wall of Grampositive bacteria and is critical for defense against certain invasive pathogens. In GBS, penicillinbinding protein 1a (PBP1a), encoded by ponA, is required for virulence. PBPs participate in cell wall synthesis and in previous studies; the absence of PBP1a was shown to result in subtle changes in the cell wall ultrastructure. Here, we examine the role of TLR2 in defense against GBS infection and the impact of mutation of ponA on TLR2-mediated host responses. We demonstrate TLR2-recognition of both WT GBS and the ponA mutant in vitro. TLR2 −/− mice were significantly more susceptible than WT mice to infection with either strain of GBS, indicating a crucial role for TLR2 in defense against GBS. Additionally, the ponA mutant was severely attenuated for virulence in both strains of mice. The mutation in ponA did not affect cytokine expression by WT or TLR2 −/− mice. These data indicate that TLR2 is required for host defense against GBS and this response is unaffected by the absence of PBP1a and the resultant changes in cell wall ultrastructure.

Streptococcus uberis strains isolated from the bovine mammary gland evade immune recognition by mammary epithelial cells, but not of macrophages

“…S. agalactiae and S. dysgalactiae activated the bovine TLR2 receptor in HEK293 cells. TLR2 activation through S. agalactiae was also previously reported [ 37 ], but has not been found by two other groups [ 40 , 41 ]. No explanation can be given to resolve this discrepancy.…”

“…These transcription factors regulate the expression of a wealth of immune genes [ 32 – 34 ]. TLR2 is known to be essential for mounting an efficient immune defence against Gram-positive bacteria [ 35 – 37 ]. Lipoproteins from these pathogens belong to its natural ligands [ 38 , 39 ].…”

TLR2-Induced IL-10 Production Impairs Neutrophil Recruitment to Infected Tissues during Neonatal Bacterial Sepsis

“…Thus, during infection in the early period of life, TLR2 is likely stimulated locally and systemically by a variety of microorganisms. Among these, the Gram-positive Group B Streptococcus (GBS) are responsible for severe forms of neonatal disease, such as pneumonia, sepsis, and meningitis (15)(16)(17). In addition to the well-characterized TLR2-mediated inflammation, data exist supporting the notion that TLR2 signaling can lead to the production of the anti-inflammatory cytokine .…”

Group B streptococcal disease in the mother and newborn—A review

“…The rare condition of MyD88 deficiency leads to a 1000-fold increase in early and late neonatal sepsis in affected infants [18]. TLR2 deficiency has been associated with predisposition to invasive bacterial infection in mice, although also protecting from lethality in invasive GBS infection, as a result of reduced cytokine responses [21]. In a study of women with pelvic inflammatory disease, the TLR2 polymorphism RS3804099 was significantly more frequent in African American women with pelvic inflammatory disease [22].…”