Toll-like receptor 2 deficiency is associated with enhanced severity of group B streptococcal disease.

Group B streptococcus (GBS) has been recognized as an ever-growing cause of serious invasive infections in nonpregnant adults, in particular, in association with severe underlying diseases. The most common manifestations include primary bacteremia, urinary tract infections, pneumonia, meningitis, peritonitis, and osteoarticular infections. Toll-like receptor-2 (TLR2) mediates host responses to gram-positive bacteria. TLR2 function was investigated in murine GBS-induced sepsis and arthritis in wild-type (wt) and TLR2-deficient (TLR2(-/-)) mice. Mice were infected with different doses of GBS (10(7), 5 x 10(6), or 10(6) CFU per mouse). Mortality, appearance of arthritis, GBS growth in the organs, and local and systemic cytokine and chemokine production were examined. TLR2(-/-) mice showed earlier and higher mortality rates and increased incidence and severity of arthritis than wt mice at all the infecting doses employed. Histopathological analysis of the joints confirmed clinical observations. TLR2(-/-) mice exhibited a higher microbial load in blood, kidneys, and joints than wt animals. In vitro experiments performed with peritoneal polymorphonuclear cells and macrophages showed a significantly lower bactericidal ability of cells from TLR2(-/-) mice. Increased systemic and local levels of interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor alpha, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-2 accompanied the more severe development of sepsis and arthritis in TLR2(-/-) mice. In conclusion, the lack of TLR2 was associated with an impaired host resistance to GBS infection, likely due to a diminished bacterial clearing and a consequent enhanced inflammatory response.